How to write a reaction in SMILES format

THE ZYMVOL BLOG

How to write a reaction in SMILES

No matter if you are a chemist or not, if you are interested in chemical notation, we hope this post will make you “smile” 🙂

 

What’s SMILES in chemistry?

Simplified Molecular-Input Line-Entry System (SMILES) is a user-friendly, chemical notation method for specifying the structure of molecules and reactions.

It consists of unambiguous, short, linear strings of characters in ASCII format, written in a language made of symbols and simple “grammar” rules.

SMILES was created to facilitate storage, retrieval and modeling of chemical structures and information in computational chemistry. Thanks to its easy and compact format, it requires a small amount of computer memory and makes it convenient for people to use it.

Plus, SMILES can be read by molecule editors and converted into two-dimensional and three-dimensional models. This is very useful, for example, when you need to study the structure of proteins such as enzymes!

 

The SMILES notation system was created in the 1980s at the Mid-Continent Ecology Division Laboratory in Duluth, Minnesota, and funded by the U.S. Environmental Protection Agency.

Afterwards, other organizations have modified and extended SMILES, which also exists in an open standard called OpenSMILES developed by the Blue Obelisk open-source chemistry community.

 

Five rules for writing SMILES

Understanding SMILES is quite easy!

First of all, keep in mind that in SMILES, each notation string represents the topological structure of a molecule or a reaction.

Similar to the concept of a graph, in SMILES the atoms of a molecule are considered as nodes, bonds are the edges, parentheses indicate branching points and numeric labels designate ring connection points.

Benzoic acid
C1=CC=C(C=C1)C(=O)O

 

And now let’s learn the five rules to write in SMILES format:

Rule 1: Atoms

In SMILES, atoms are represented by their atomic symbols: O for oxygen, Br for bromine, and so on, using lower case for the second letter in two-character symbols.

For elements in the «organic subset» (B, C, N, O, P, S, F, Cl, Br, and I) and with their lowest normal valence, attached hydrogens usually don’t need to be written. That’s why methane (CH4) can be written simply as C.

However, all elements and organic ones with other valences must be described in brackets as follows:

 

[OH3+]

Inside brackets, any attached hydrogens have to be indicated by an «H», followed by a digit.

 

[Fe+3]

Meanwhile, formal charges must always be specified by the symbol «+» or «-«, followed by a digit.

 

Rule 2: Bonds

Bonds between atoms are represented by different symbols depending on the type:

 

For single bonds

=

For double bonds (C=O formaldehyde)

#

For triple bonds (C#N hydrogen cyanide)

:

For aromatic bonds.

 

But atoms that are next to each other are assumed to be connected by a single or aromatic bond, so these two may always be omitted, as in ethanol:

 

CCO

 

Rule 3: Branches

In case of molecules with branches, you just have to know that branches are enclosed in parentheses «( )» and the bond that joins the branch to the “parent chain” has to appear inside the parentheses.

Have a look at triethylamine. Its SMILES is CCN(CC)CC, where (CC) refers to the branch that starts from the nitrogen atom:

 

CCN(CC)CC

 

Rule 4: Cyclic structures

Molecules that are shaped in a ring –like aromatic molecules– are also written linearly.

Ring opening and closure are indicated by a digit that follows

 

the atomic symbol at each opening/closure. See for example cyclohexane:

 

C1CCCCC1

 

Curiously, different notations can represent the same cyclic structure, depending on where the ring starts to be written, and all are equally valid.

For example, cyclohexene (see image below) can be written like:

 

C1=CCCCC1
C=1CCCCC1
C1CCCCC=1
C=1CCCCC=1

 

 

All are equally valid and just differ in the ring’s starting point.

Atoms in aromatic rings are written in lower case to be differentiated, as in benzene. This SMILES represents an hexagonal ring of six carbons with one hydrogen atom attached to each:

 

c1ccccc1

 

Rule 5: Disconnected structures

SMILES does not only serve for writing single molecules. You can also represent disconnected compounds or, in other words, atoms not bonded to each other.

But how?

Disconnected structures are written as individual structures separated by a period: «.». They are just adjacent atoms and the order in which ions or ligands are listed is arbitrary. 

For example, sodium chloride (table salt) is an ionic compound and its SMILES looks like this:

 

[Na+].[Cl-]

 

Are you starting to get it?

Thanks to these five rules, chemists can write very complex topological structures and unique strings for every existing molecular structure.

 

How can SMILES represent unique structures?

As you might have guessed from the rules, SMILES strings describe the two-dimensional graphs that chemists normally use to represent molecules.

Three-dimensional structures are also obtained from SMILES strings with energy-minimization approaches, which basically predict protein structure based on the most efficient arrangement of the atoms and bonds of the molecule in terms of free energy.

But how is this notation method so precise, being the diversity of molecules so wide and complex?

As mentioned before, there is more than one SMILES for some molecules.

For example: OCC, C-C-O and C(O)C are all generic SMILES for ethanol. Generic SMILES do not take into account chiral or isotopic information. 

How has this been solved? With canonicalization: algorithms that generate one single specific SMILES among all valid possibilities. 

The unique SMILE takes into account chiral and isotopic specifications. For the previous example, all previous generic SMILES would be converted into the unique smile CCO, a universal identifier for a specific chemical structure.

 

Using a SMILES generator

Understanding the SMILES “language” is always going to be useful for those who have to deal with chemical notations in computational format.

But don’t worry, you don’t need to learn SMILES by heart, because there are tools to generate SMILES.

For example, when our company launched ZYMSCAN, we knew we wanted to use a SMILES generator to make the user experience as easy as possible for chemists.

ZYMSCAN was created to help users know if a certain reaction can be performed enzymatically without wasting time going through other methods.

It consists of three simple steps, which start with submitting the substrate and product SMILES of the reaction of interest.

Thanks to SMILES’ unambiguous format, we are sure to be understanding the user’s very specific needs correctly, because each molecule’s notation is unique.

 

Are there alternatives to SMILES?

SMILES is not the only linear notation. The International Union of Pure and Applied Chemistry (IUPAC) created its own system to standardize the identification for chemical databases: InChi

As SMILES, it is also open source and freely accessible. Both are the most important and commonly used line notations today, and are complementary to each other. 

The big differences are that SMILES is not an identifier, but a chemical representation format. Besides, while InChI is well-documented and standardized through IUPAC, there is no up-to-date specification documentation for SMILES.

The latter is the main reason why the US Environmental Protection Agency, which created SMILES, is working on the interoperability of this format. The aim is to establish a formalized specification to promote the exchange of scientific information together with IUPAC’s InChi.


What's an EC Number & how to interpret it

THE ZYMVOL BLOG

What's an EC Number & how to interpret it

You might have heard about EC numbers.

They are widely used in biochemistry and molecular biology to provide a clear and standardized way to refer to enzymes, especially in scientific literature and databases.

This classification method helps us differentiate among thousands of enzyme types that, otherwise, would be very hard to recognise by everyone.

Because giving enzymes arbitrary, common names worked well when only a few were known.

But now, after more than a century of enzyme discovery, naming more than 8.000 enzymes would be simply impossible.

Only a few names have survived in our common language, such as cellulase (EC 3.2.1.4), papain (EC 3.4.22.2) or proteases (all EC 3.4. numbers). For the rest, EC numbers are our only and best way to talk about the broad world of biocatalysis.

 

What’s an EC Number?

The Enzyme Commission (EC) number is a nomenclature system based on the chemical reactions that these proteins catalyze.

It was developed by the International Union of Biochemistry and Molecular Biology (IUBMB) and consists of a numerical classification scheme where each number is associated with an enzyme-catalyzed reaction.

Note that each EC number is not associated with a specific enzyme, because in nature we can find different enzymes that catalyze the same reaction.

 

How to read an EC number

An EC number is typically represented as a sequence of four numbers separated by periods, which is linked to a recommended name. For example, EC 1.1.1.1 (alcohol dehydrogenase).

Let’s see what each of these four numbers represents:

First Number: The type of reaction or enzyme class

The first number indicates the enzyme class, based on the type of reaction each of these classes catalyzes. There are seven main classes:

EC 1: Oxidoreductases – Enzymes that catalyze oxidation-reduction reactions.

EC 2: Transferases – Enzymes that transfer a functional group (e.g., a methyl or phosphate group).

EC 3: Hydrolases – Enzymes that catalyze the hydrolysis of various bonds.

EC 4: Lyases – Enzymes that break various chemical bonds by means other than hydrolysis and oxidation, often forming a new double bond or ring structure.

EC 5: Isomerases – Enzymes that catalyze the transfer of groups within molecules to yield isomeric forms.

EC 6: Ligases – Enzymes that join two molecules together, typically using ATP.

EC 7: Translocases – Enzymes that catalyze the movement of ions or molecules across membranes or their separation within membranes.

Second and third numbers: Enzyme subclass and sub-subclass

These two numbers provide more detail about the type of molecular group, bond or product involved in the enzyme-catalyzed reaction, narrowing down the specificity of the reaction.

Fourth Number: Enzyme identification

This is the serial number of the enzyme. It represents the specific enzyme identity, related to specific metabolites and/or cofactors involved in the enzyme-catalyzed reaction.

 

A couple of examples

Now that you know the basics, let’s see how this looks put into practice.

Let’s start with the first number that appears in the classification:

 

EC 1.1.1.1

– The first «1» indicates that it’s an oxidoreductase (an enzyme that catalyzes the transfer of electrons from one molecule, the reductant, to another, the oxidant).

– The second «1» specifies that it acts on the CH-OH group of donors.

– The third «1» indicates that NAD+ or NADP+ is the acceptor.

– The final «1» is the specific serial number for this enzyme in its group, which is given the recommended name of alcohol dehydrogenase.

 

See? That wasn’t so hard.

Now let’s mix it up a little and look at another one.

 

EC 6.3.2.24

– Here, the first «6» indicates that it’s a ligase (an enzyme that catalyzes the joining of two molecules by forming a new chemical bond).

– The second number is «3» and specifies that the type of bonds that forms are carbon-nitrogen.

– The third number is «2» and specifies that the types of molecules that are bonded are an acid and an amino-acid.

– The last number is «24», the specific serial number for this enzyme in its group, and specifies that the two amino acids bond catalyzed by the enzyme is tyrosine—arginine, which gives the recommended name of tyrosine—arginine ligase.

 

Are you starting to get the hang of it? This classification is quite easy to follow. And, don’t worry, nobody expects you to know all these numbers by heart. You just need to understand the rationale behind. After all, EC numbers are here to make our lives easier!

 

Is there a complete enzyme classification by EC number?

Of course! People have always loved to bring order to chaos.

In this case, it is the IUBMB who provides an approved and updated enzyme classification list based on the EC number nomenclature: the ExplorEnz Enzyme Database.

The first edition was published in 1992. From then on, 29 more supplements or edits have been added to that initial version to register all the new enzymes discovered and modifications needed.

You can dive into its tree structure, expanding each list of the classes, subclasses, sub-subclasses and serial numbers, to have a deeper view of the entire classification.

 

How to find the enzyme that I’m searching for?

If you’ve ever had to find out if a certain reaction can be performed enzymatically, you may know the answer does not come easily navigating through the EC numbers database on your own.

This is a very common problem for industries or research groups considering the possibility of doing a chemical process with enzymes, who usually spend too much time searching in the literature or asking other colleagues.

In those cases, a quick and simple answer in the form of an EC number can save a lot of time and open the door to innovative projects that were long stuck.

At ZYMVOL we developed ZYMSCAN with that in mind: if a chemist wants to know if their reaction can be done enzymatically, they just have to submit their reaction and ZYMSCAN will confirm if it can be done with biocatalysis. In case it can, they will receive an email with the EC number of the enzyme family that matches the reaction.

 

As you can see, an EC number can be very useful not only in scientific literature, but also in applied chemistry; and now you know how to interpret it!


How enzymes improved… detergents

THE ZYMVOL BLOG

How enzymes improved... detergents

Detergents were probably one of the first products that showed the world that enzymes – those proteins that perfectly catalyze the chemical reactions in our bodies – could play an even bigger role in our daily lives.

When detergent manufacturers started incorporating enzymes into their formulations, consumers no longer needed high temperatures and long, fabric-damaging processes to completely clean off dirt from their clothes. 

Enzymes like proteases, amylases and lipases helped remove even the most difficult stains; and since these biocatalysts worked best under mild conditions, families could opt-out from using hot water and clothes would still get cleaned. 

Detergents have shown us that enzymes can revolutionize a whole industry; even to the point that, nowadays, we cannot imagine life without them.

There’s a lot to learn from this landmark of innovation. 

Let’s start from the beginning.

The Discovery

Our fresh laundry owes much to Otto Röhm, a German pharmacist from the late 19th century that, on December 11th 1913, patented the first detergent with enzymes: Burnus.

Otto was working for the Stuttgart city gasworks, where his job focused on leather treatment, when he realized that the trypsin extracted from pig’s pancreas could help dissolve clothes’ stains.

Even though “Burnus” didn’t succeed in the market and needed to be improved due to the low activity of the enzyme, it set a precedent for the future of modern cleaning supplies.

50 years later, enzyme detergents exploded in popularity and gradually introduced different types of enzymes to their formulations.

Since then, washing needs lower temperature, less water and diverse types of stains are removed efficiently, saving energy and time.

The success was such that, nowadays, the detergent business is one of the largest single market places for enzymes.

 

An enzyme for every stain

Detergent enzymes detach and degrade all kinds of dirt by breaking down molecules’ chemical bonds. They’re all known as hydrolases, because they need water to do such reactions. But did you know there’s a specific type of enzyme for every kind of dirt stain?

  • Proteases degrade stains composed of protein by breaking the peptide chains. Historically, first enzymes to be used in detergents.
  • Amylases break down starch-based stains and also contribute to maintaining white fabrics color.
  • Lipases attack fat-based stains hydrolyzing triglycerides to simpler fats that can be dissolved.
  • Pectinases eliminate stains from other types of complex sugars present in fruits, vegetables, jams and juices.
  • Mannanases remove stains from milkshakes or ice cream and personal hygiene products containing mannans, a type of complex sugars used as a thickening agent.
  • Cellulases improve cotton and linen fabrics cleanness and softness by breaking down cellulose fibers and hindering dirt particles attachment.

Nowadays, enzyme detergents profit from the combined effect of multi-enzyme systems and are more sustainable thanks to the substitution of traditional detergent components that are harmful for the environment.

But their impact goes way beyond removing stains from clothes.

  • Their use at industrial dishwashers promote leftovers decomposition, which protects machines and saves the recirculating water that used to need replacement more often before.
  • At hospitals, clothes stay white because proteases can remove blood from fabrics. But they also benefit from enzyme action for properly cleaning medical devices, which need different cleaning conditions than normal sterilization machines.
  • Safety at commercial kitchens wouldn’t be the same without lipases. These enzymes are great at removing fat from the floor, which not only cleans it, but helps prevent accidents.

Amazing, right?

However, if their versatility wasn’t enough, there’s one more reason why enzymes have become a powerful ally in the cleaning industry: they make detergents more sustainable.

 

How enzyme detergents help us go green

The need to reduce our environmental footprint without compromising efficiency has found in enzymes a great alternative to traditional chemical processes.

As proteins, enzymes are biodegradable and can substitute toxic and pollutant compounds, like phosphates and phosphonates, enhancing the protection of our health and the environment.

Plus, since biocatalysis can take place at mild conditions of temperature and pH, this can reduce the environmental impact and energy cost of the common use of washing machines.

Here are two clear cases of enzymes helping reduce the environmental impact of detergents:

 

Cold-active enzymes

We’ve all heard the same story: to get rid of difficult stains, you need to use hot water.

But, if you’ve spent a long time relying on this advice for your weekly washing, you might have realized that setting your machine to the highest temperature is not sustainable at all.

Sensitive fabrics might get damaged. Some might lose their color.

And worst of all, electricity bills skyrocket.

This is because, normally, most of the electricity a washing machine uses goes exclusively to heating the water.

But the good news is, for most types of dirt, you don’t need to use hot water to obtain good results. And even if you’re faced with a difficult stain, enzymes can help!

The introduction of cold-active enzymes in detergent products have allowed washing temperatures to be reduced from 60-40ºC to 30°C without compromising on cleanliness.

These enzymes come from psychrophilic microorganisms, which are found in cold regions like the Antarctic and Arctic, glaciers and/or deep sea sediments.

By washing at low temperature, CO2 saving potential in the United States and Europe alone is around 32 million tons annually, equal to the emissions of 8 million cars (OECD).

The only drawback? Natural cold-active enzymes are not always as abundant and stable as the industry needs.

But no worries: there’s evidence that protein engineering can genetically improve psychrophilic strains, enhancing enzymes and making the use of cold-active enzymes easier for everyone.

 

Compact detergents

Powder or liquid, applying it with a dispenser or in individual pods or tablets. No matter the format, over the years formulations have progressed to lower the volume of detergent needed for the same size of wash load.

Thanks to their high activity at low concentrations, tiny amounts of enzymes are enough for compact detergents to wash as efficiently as the others.

Besides, they do not disappear or lose their activity, but activate the reactions that ease dirt removal over and over again during wash time.

This has made possible for the average dosage of detergent to be reduced by 50% and achieve savings of 30 millions tons in Europe over the past two decades (AISE).

Plus, it doesn’t end there:

  • Smaller doses of detergent need less amount of water for washing and can eliminate the need for a pre-wash cycle, which leads to significant water savings.
  • Compact detergents fit in smaller packaging, which reduces the amount of materials needed for storage and transportation. 

Smaller packaging means more packages transported per vehicle along its life cycle. And less trips needed mean, of course, less CO2 emissions!

Can we make enzyme detergents… even better?

Here’s a tricky question: modern detergents contain enzyme mixes that include proteases to degrade protein stains. But, since enzymes are also proteins, how come they don’t degrade themselves?

The answer is simple. By adding “inhibitors” to detergent formulations, scientists can keep proteases deactivated when it’s stored, so that they only work when mixed with water.

But there’s a catch.

Most common inhibitors contain boron, which is toxic for plants and insects. Each time we do our laundry, we are slowly liberating this element into the environment through the discarded water.

So a pretty good solution -which is using enzymes to make detergents work better- is, at the same time, creating a problem we want to avoid: the pollution of our environment!

 

The IDEA-PS Project

At ZYMVOL, we’re proud to be part of a project that aims to solve this issue in the best way we know: using our computer power (and our team’s smart brains!).

Together with biochemical company CYGYC BIOCON (BIOKATAL), we’re developing a new computational platform that can help us search for more sustainable enzyme inhibitors for detergent formulations.

ZYMVOL Senior Researcher, Dr. Brian Jiménez Garcia, is the primary investigator leading this project, which we have named “IDEA-PS”*. You can read more about it in the news article we released last year.

As our colleague Dr. Jiménez Garcia points out: “We hope that with this software, we will be able to help scientists make more effective formulations that will save resources, energy and water”.

Isn’t that a great goal to work towards?

 


*IDEA-PS is funded by ACCIÓ Tecniospring INDUSTRY programme and MSCActions.


The Evolution of Directed Evolution

THE ZYMVOL BLOG

The Evolution of Directed Evolution

Life on Earth has evolved over millions of years thanks to genetic variation

Imagine a tree species adapted to drought that starts to face frequent and abundant rains. 

The whole species would disappear!

Unless… There were a few individuals able to face the new situation because of slight, random genetic differences, allowing them to adapt to the changing environmental conditions.

Individuals with more favorable traits to a given environment will survive and reproduce more than others, transferring their genes to the next generation. 

This process, known as natural selection, is the major driver of evolution. But selection can also be fostered, and even controlled, in search for specific new traits by humans.

We started to learn how to intervene in the natural process of evolution long before calling it artificial selection or selective breeding.

Developing agriculture and livestock, we became a decisive selective force that kept, across generations, those traits of cattle and vegetables favorable to human sedentarism subsistence, like yield, resistance.

We were basically mimicking nature or ‘biomimicking’ at a pace that was enough to foster human civilization progress at that time. 

Nowadays, we are able to control this process in much more precise, sophisticated and faster ways.

A Nobel-Award Winning Workflow

Evolution occurs at an ample time scale, which is not compatible with fast changing industries and human lifetimes span.

This is where Directed Evolution comes in.

Directed Evolution  speeds up the natural selection process – in an iterative workflow that takes place in controlled laboratory conditions either in vivo (within microorganisms, that reproduce very fast) or in vitro (in artificial cell-like simple structures):

  1. Generation of genetic variation for the desired target enzyme through  different mutagenesis techniques.
  2. Differences in fitness are screened and deliberately selected for the desired conditions.
  3. Inheritance of the selected traits is substituted by the artificial amplification of the genes encoding those proteins with improved catalytic properties.

This cycle can be repeated several times, each starting with the last better performing obtained variant, to direct evolution towards the chosen goal – for example, improved performance or new catalytic properties –, optimizing the new functions up to a desired level.

Did you know…?

Frances H Arnold, professor of Chemical Engineering, Bioengineering and Biochemistry at Caltech (US), was awarded in 2018 the Nobel Prize in Chemistry for the conception and development of this directed evolution workflow.

Arnold shared the prize with other two scientists, George P Smith and Sir Gregory P Winter, for developing a different technique for binding-proteins selection, advantageous in the field of Immunology.

So why was Directed Evolution such a breakthrough?

Single enzyme types can be selected for specific biocatalytic properties and, then, evolved towards new functions, some of them not even existing in nature. 

Directed evolution is used as a research tool to study enzyme evolution, but specially, as a revolutionary method to obtain biocatalysts for industrial processes.

These natural catalysts accomplish a wide array of chemical reactions that take part in the production of a broad variety of products, such as drugs, perfumes, detergents or food.

For example, one of the widest known enzymes used in industry is lactase, which degrades lactose from milk, producing lactose-free milk as a result, a suitable option for those who cannot digest that sugar, normally present in dairy products.

Directed evolution has become an ally of industrial innovation, adapting and optimizing the reactions of enzymes towards precise and desired industrial goals regarding speed, substrate, type of reaction and more.

Beyond Bio-mimicking

Nowadays, technological advances in different areas, such as biotechnology, bioinformatics and IT, are allowing us to perform, in an increasingly improved way, directed evolution in silico, that is, in the computer

Computational enzyme engineering uses bioinformatics and molecular modeling tools to redesign existing enzymes performing the directed evolution process in silico.

Performing these first rounds in the computer (by virtually screening millions of variants) saves time and resources compared to traditional lab work. 

It also opened the door for rational design: protein design through algorithms and simulations that allow to obtain, in a short period, desired enzyme properties that are not easily reachable by the conventional workflow nor found in nature.

Big advances are taking place in order to combine both in silico methods with experimental data.

We are in the fascinating process of better knowing how enzymes work and constantly improving the accuracy to detect which amino acids can be mutated to be beneficial. But the progress done so far has already boosted the industrial use of enzymes since its onset 30 years ago.

It’s impressive how we’ve leveraged the power of evolution, as France Arnold emphasized at the end of her Nobel Lecture in 2018:

“I am continually amazed at the ease with which evolution innovates (…) Instead of asking what enzymes do in the natural world, we can now ask, “What might they do?” Enzymes will perform chemistry in more ways than we could have imagined, especially when we use evolution to unleash their latent potential.”

Frances Arnold, professor of Chemical Engineering, Bioengineering and Biochemistry at Caltech


References

[1] Heckmann, C. M. and Paradisi, F. (2020). Looking Back: A Short History of the Discovery of Enzymes and How They Became Powerful Chemical Tools. ChemCatChem, 2020, 12: 6082 – 6102.
[2] Chen, K. and Arnold, F.H. (1993). Tuning the activity of an enzyme for unusual environments: sequential random mutagenesis of subtilisin E for catalysis in dimethylformamide. Proc Natl Acad Sci USA. 90:5618-5622.
[3] Tawfik, D.S. and Griffiths, A.D. (1998). Man-made cell-like compartments for molecular evolution. Nat Biotechnol. 16:652-656
[4] The Nobel Prize in Chemistry 2018. NobelPrize.org. Nobel Prize Outreach AB 2022. Mon. 3 Oct 2022
[5] Jäckel, C., Kast, P. and Hilvert, D. (2008.) Protein design by directed evolution. Annu Rev Biophys. 37:153-173.
[6] Arnold, F.H. (2019). Innovation by Evolution: Bringing New Chemistry to Life (Nobel Lecture). Angew. Chem. Int. Ed. 58: 14420 – 14426
[7] McLure, R.J., Radford, S.E. and Brockwell, D.J. (2022). High-throughput directed evolution: a golden era for protein science. Trends in Chemistry. 4: 278-291.


A look at our Enzyme Technology: Molecular Modeling

This post has been written by ZYMVOL's Senior Researchers Marina Cañellas and Lur Alonso.

 

Zymvol’s core technology is Molecular Modeling, which – along with bioinformatics – allows us to understand the mechanistic details under enzymatic function and use the generated knowledge to search and tailor biocatalysts towards improved properties.

In this way, by integrating molecular modeling-based strategies at distinct levels of theory, we can identify the best target enzymes and perform their custom design in less than one month!

So, what is Molecular Modeling?

Molecular Modeling refers to a collection of in silico methods that model or mimic the behavior of molecules, ions and/or particles (Nature Subjects). Their main goal is to provide knowledge on the chemistry, structure, dynamics and function of these systems. 

By definition, In silico refers to “conducted or produced by means of computer modelling or computer simulation” (Oxford Dictionary). Simply put, as these methods require huge amounts of calculations, they are performed by computers.

Molecular Modeling has a wide range of applications in many different areas:  computational chemistry, computational biology, drug design, material science… and for this reason it has become a rapidly growing field during the last decades. 

The large variety of systems that can be modeled range from small chemical systems (like the reaction mechanism between two substrates) to larger biological molecules (such as enzymes, antibodies or DNA) and material/molecular assemblies (like supramolecular polymers (Bochiccio, 2017; Frederix, 2018), protein-based assemblies (Soni, 2017), and molecular machines (Aprahamian, 2020).

Although many limitations still exist, they have shed light on some features like functions, processes, and catalytic pathways.

QM and MM

Because of the high complexity underneath molecular systems, such as enzyme-catalyzed reactions, there is not a single in silico technique that suffices for their full modeling. In this way, two main categories of computational methods have been developed at different levels of description: 

  • Those describing systems from an electronic point of view (Quantum Mechanics (QM) methods, this is the deepest level of accuracy to study a system!)
  • Those that describe systems at the atomic level (Molecular Mechanics (MM) methods).

QM methods provide an accurate representation of the system, enabling the description of reaction mechanisms at the electron level, but are computationally very expensive.

On the other hand, MM methods allow the study of larger molecules like proteins, enabling sampling the overall system flexibility, but cannot represent bond-breaking/bond-forming events. As a solution to this issue, the benefits of both strategies can synergize into hybrid schemes, such as combined Quantum Mechanics/Molecular Mechanics methods (QM/MM), enabling the accurate description of large biological phenomena and reactions. QM/MM was awarded with the Nobel Prize in 2013 to scientists Karplus, Levitt, and Warshel.

Adapted from Dr. Marina Cañellas PhD thesis “In silico molecular modelling and design
of heme-containing peroxidases for industrial applications” 2018.

 

The benefits of Molecular Modeling

Why do we think that relying only on bioinformatics is not enough?

Of course, there are some perks to it.

  • Allows to simulate an entire chemical system in the computer
  • It has unique potential to offer detailed atomic-level insights into the studied systems 
  • Allows to predict new mutant variants beyond currently available data.
  • Allows to perform millions of screening/mutations in one day, saving up to 90% of time (compared to experimental procedure). 
  • Saves resources since only a low number of enzymes are tested in the lab (maximum of 300 enzymes tested in the lab with Zymvol’s technology instead of up to millions using exclusively experimental approaches)

As pointed out before, Molecular Modeling techniques are always complemented with sequence-based strategies; the increasing field of bioinformatics complements the predictions and adds new hints hidden on the protein sequence! 

Bioinformatics evaluates the vast amount of data collected daily worldwide and extracts extremely valuable information by applying the proper tools and algorithms. 

Molecular modeling complements wet lab experiments. The way of maximizing success and development in our services Enzyme Search and In silico design is through the close collaboration between dry and wet lab. Considering these two areas as iterative approaches allows scientists to gather a deeper and faster understanding of, in this case, biocatalysis. While computational predictions need to be validated by experimental techniques, wet lab experiments can also benefit from computational approaches by reducing the research time and costs and giving valuable atomic-level insights. In this way, by analyzing huge datasets (sequences, mutant libraries, enzymatic properties, …), lab work is significantly reduced. This enables scientists to obtain results in shorter times and accelerates research/industrial projects, which is of imperious importance for the Industrial Sector (Truppo 2017).

Molecular Modeling in use

Due to the exponential increase that computational resources and strategies have undergone in the last decade, in silico simulations have gained a spot guiding the experimental work in a wide range of areas. (Check the following references for more information on these topics: Hollingsworth & Dror, 2018, Schwaigerlehner et al., 2018, Blog article Ebejer and Baron 2020, as well as more trend research like the one related to COVID19 (Talk by Strauch, 2021)). 

Some fields that are benefited by these in silico methodologies include:

  • Drug discovery (disease mechanisms)
  • Neuroscience (for example, protein-protein interactions)
  • Advanced therapies (for example, antibody engineering)
  • Biocatalysis (for example, directed evolution)

Some practical examples:

  • Elucidate enzymatic mechanisms, understanding enzymes’ catalytic power and enzyme design.
  • Simulation of binding-free energies of small molecules (e.g drugs to their targets).
  • Search for wild type enzymes to perform a particular non-natural reaction.

Getting the best out of Molecular Modeling

As it has been stated, Molecular Modeling is one of the most important approaches we use to provide our Enzyme Search and In Silico Design services. Thanks to our innovative approach, at ZYMVOL we are able to take into account the following features:

  • Solvent effects (by incorporating explicit waters in our simulations) 
  • Quantic effects 
  • Dynamic changes of the protein backbone (backbone flexibility)
  • Distant mutations
  • Side chain flexibility

 

 

Normally, it's hard to find companies who work with all these features, since techniques are very expensive, time consuming or require high specialization. 

The truth is that in this area, the customer moves in the trade off triangle of price-time-expertise: either techniques are very expensive (and/or time-consuming) or require scientists with outstanding degree of specialization to successfully carry out projects. 

What you usually find in the market is:

  • Companies relying only in bioinformatics and experimental work (↑time, ↑price, ↓specific expertise)
  • Companies offering only experimental approach (↑time, ↑price, ↓specific expertise)
  • Companies that offer excellent software, but it is very difficult to achieve quick, reliable results without the assistance of an expert.  (↑time, ↓price, ↓specific expertise).

However, taking all of these features into account is truly beneficial, as it means:

  • More realistic simulations
  • More accurate results and with the unique advantage 
  • The possibility of obtain results in significant short times

Molecular Modeling is a truly powerful tool and it has contributed significantly to our enzyme discovery and design projects. Thanks to it, we can help many industries transition to the use of biocatalysts and make the industry greener.

Do you still have questions related to molecular modeling? Drop us an email: info@zymvol.com

 


References:

Aprahamian, I. (March 3, 2020) The Future of Molecular Machines. ACS Cent. Sci., 6(3), 347-359

Bochicchio, D.; Pavan, G.M. (February 11, 2018) Molecular modelling of supramolecular polymers. Advances in Physics:X, 3(1)

Ebejer, J.P; Baron, B. (June 14, 2020) Dry- and wet-lab research: two sides of the same coin. Times of Malta. https://timesofmalta.com/articles/view/dry-and-wet-lab-research-two-sides-of-the-same-coin.798297

Frederix, P.W.J.M.; Patmanidis, I.; Marrink, S.J. (April 24, 2018). Molecular simulations of self-assembling bio-inspired supramolecular systems and their connection to experiments. Chem. Soc. Rev., 47, 3470-3489

Hollingsworth, S.A.; Dror, R.O. (Sept 19, 2018) Molecular dynamics simulation for all. Neuron, 99(6), 1129-1143

Nature. Molecular Modelling. https://www.nature.com/subjects/molecular-modelling

Soni, N.; Mashusudhan, M.S. (June, 2017) Computational modeling of protein assemblies. Current Opinion in Structural Biology, 44, 179-189

Schwaigerlehner, L; Pechlaner, M; Mayrhofer, P; Oostenbrink, C; Kunert, R. (May 11, 2018) Lessons learned from merging wet lab experiments with molecular simulation to improve mAb humanization. Peds, 31(7-8), 257-265

Truppo, M.D. (April 18, 2017) Biocatalysis in the Pharmaceutical Industry: The Need for Speed. ACS Med Chem Lett. 8(5): 476-480


Why is Green Chemistry important? Origins and Industry Impact

For the past few decades, the scientific community as well as society as a whole has raised its voice on the impact our actions have on the environment, pressing authorities and looking for solutions to address the problem. One of the main focuses has been set on Chemistry, as many “traditional” chemical processes are not sustainable in the long run, with devastating consequences for the environment and quality of life.

In this context, there’s a term that has been slowly, but steadily, gaining traction: Green Chemistry

As the International Union of Pure and Applied Chemistry (IUPAC) puts it, Green Chemistry (also known as Sustainable Chemistry) encompasses the “invention, design, and application of chemical products and processes to reduce or to eliminate the use and generation of hazardous substances”.

But what does this all mean? Why is green chemistry important and how does it contribute to the world’s sustainable development?

Let’s start by going back in history…

The Origins of Green Chemistry

According to the American Chemical Society (ACS), the term “Green Chemistry” was first coined by the US Environmental Protection Agency – Office of Pollution Prevention and Toxins around the 1990s.

The idea of a greater consciousness regarding chemistry had been gaining power since the 60s and 70s, however, it was mostly focused on banning dangerous toxins like DDT and “cleaning up” the aftermath of certain chemical activities. It was not until the 80s and 90s that scientists started thinking differently about their way of doing chemistry, shifting the focus on how to prevent pollution before it even took place.

Then, in 1998, two scientists named Paul Anastas and John C. Warner published what today is popularly known as the «Twelve Principles of Green Chemistry».

The Twelve Principles of Green Chemistry

First published in the book “Green Chemistry: Theory and Practice”, the Twelve Principles of Green Chemistry is a set of guidelines that other chemists can consult to work towards a more sustainable chemistry. The book marked a new era, by helping consolidate a movement that was destined to define how modern chemistry is made.

The principles highlighted in Anastas and Warner’s book are:

  1. Waste Prevention
  2. Atom Economy
  3. Less Hazardous Chemical Syntheses
  4. Designing Safer Chemicals
  5. Safer Solvents and Auxiliaries
  6. Design for Energy Efficiency
  7. Use of Renewable Feedstocks
  8. Reduce Derivatives
  9. Catalysis
  10. Design for Degradation
  11. Real-time analysis for Pollution Prevention
  12. Safer Chemistry for Accident Prevention

Green Chemistry in Industry

Now that sustainability is on everybody’s top-of-mind, Green Chemistry is more important than ever. Just think about the amount of industries that rely on chemistry and whose activity has a great impact on the environment: pharma, agriculture, colorants, materials, consumer products… to name a few. 

This in part is due to the clear increase in awareness about environmental pollution. Especially since the last decades, people are becoming aware that we, as humans, are stressing the planet’s finite resources, and acknowledging that our consumption and waste have to go somewhere. And the current COVID crisis has consolidated this feeling. Just to mention some facts, there is fair evidence about:

If you watch the news, you might have noticed that some institutions are working non-stop to keep this issue present, like the World Economic Forum, or the United Nations, with the  Sustainable Development Goals and the Paris Agreement.

And special laws and regulations are being developed to promote more environmentally friendly, sustainable production processes and industries: REACH normative in European Union, ISO 14001, to name some of them.

In parallel, consumers are concerned about the impact the products they buy have in the environment and in their own bodies. Multiple initiatives inviting consumers to choose more “consciously” are nowadays on the front line, and they are demanding products that are respectful in the whole production chain: from manufacturing to recyclability. 

Having said all this, perhaps you are not very sure yet about the difference between green chemistry and general chemistry. The best way to describe it is that Green Chemistry’s main goal is to achieve the same or equivalent chemical reactions with a decrease in environmental damage.

And how is this accomplished?

Some techniques that are used for this aim include:

  • Catalysis: as mentioned in our first blog post, catalysis is the process of increasing a chemical reaction’s rate by the addition of an element denominated catalyst (like enzymes!), that is not consumed during the reaction and therefore can act repeatedly.
  • Synthetic biology: by applying engineering principles, the goal is to redesign and create new biological systems with the aim of providing novel solutions. Examples of this could be the creation of lab-grown meat, synthetic insulin or biofuels produced by algae.
  • Chemical synthesis: as the Nature journal definition says, chemical synthesis is “the process by which one or more chemical reactions are performed with the aim of converting a reactant or starting material into a product or multiple products”.

Why are industrial enzymes an example of Green Chemistry?

Maybe you are still wondering how green chemistry can help decrease pollution.

Like we mentioned earlier, Green Chemistry focuses on sustainability by looking for ways of preventing pollution, hazardous activity and resource waste. That’s why the use of industrial enzymes is such a sought-after solution for many companies who want to shift to greener production processes.

As biocatalysts, enzymes have a set of properties more beneficial than their non-enzymatic counterparts:

They are highly selective and specific, which allows chemists to have more control over their desired results.

They are effective under mild temperatures, which means significant energy savings.

They do not generate toxic waste.

As you can see, enzymes are pretty powerful! The main problem is adapting these enzymes to an industrial setting, which usually means tweaking the structure of an already existing enzyme to give it new features and make it work under certain conditions.That’s why at Zymvol we work to expand the use of green chemistry by creating custom-made enzymes for different industries. With some time and effort, we can make the world become a little bit greener.

References:

American Chemical Society. Green Chemistry History. https://www.acs.org/content/acs/en/greenchemistry/what-is-green-chemistry/history-of-green-chemistry.html 

CompoundChem (September 24, 2015). The Twelve Principles of Green Chemistry: What it is & Why it Matters. https://www.compoundchem.com/2015/09/24/green-chemistry/

Nature. Chemical Synthesis. https://www.nature.com/subjects/synthesis 

European Environment Agency (March 25, 2021) Synthetic biology and the environment. https://www.eea.europa.eu/publications/synthetic-biology-and-the-environment 

Aatresh, A.; Cumbers, J. (September 22, 2019) Can Synthetic Biology Make Insulin Faster, Better and Cheaper?. Synbiobeta. https://synbiobeta.com/can-synthetic-biology-make-insulin-faster-better-and-cheaper/ 

Straathof, A.J.J.; Adlercreutz, P. (2000). Applied Biocatalysis (2nd Ed.). CRC Press.

For the past few decades, the scientific community as well as society as a whole has raised its voice on the impact our actions have on the environment, pressing authorities and looking for solutions to address the problem. One of the main focuses has been set on Chemistry, as many “traditional” chemical processes are not sustainable in the long run, with devastating consequences for the environment and quality of life.

In this context, there’s a term that has been slowly, but steadily, gaining traction: Green Chemistry

As the International Union of Pure and Applied Chemistry (IUPAC) puts it, Green Chemistry (also known as Sustainable Chemistry) encompasses the “invention, design, and application of chemical products and processes to reduce or to eliminate the use and generation of hazardous substances”.

But what does this all mean? Why is green chemistry important and how does it contribute to the world’s sustainable development?

Let’s start by going back in history…

The Origins of Green Chemistry

According to the American Chemical Society (ACS), the term “Green Chemistry” was first coined by the US Environmental Protection Agency – Office of Pollution Prevention and Toxins around the 1990s.

The idea of a greater consciousness regarding chemistry had been gaining power since the 60s and 70s, however, it was mostly focused on banning dangerous toxins like DDT and “cleaning up” the aftermath of certain chemical activities. It was not until the 80s and 90s that scientists started thinking differently about their way of doing chemistry, shifting the focus on how to prevent pollution before it even took place.

Then, in 1998, two scientists named Paul Anastas and John C. Warner published what today is popularly known as the «Twelve Principles of Green Chemistry».

The Twelve Principles of Green Chemistry

First published in the book “Green Chemistry: Theory and Practice”, the Twelve Principles of Green Chemistry is a set of guidelines that other chemists can consult to work towards a more sustainable chemistry. The book marked a new era, by helping consolidate a movement that was destined to define how modern chemistry is made.

The principles highlighted in Anastas and Warner’s book are:

  1. Waste Prevention
  2. Atom Economy
  3. Less Hazardous Chemical Syntheses
  4. Designing Safer Chemicals
  5. Safer Solvents and Auxiliaries
  6. Design for Energy Efficiency
  7. Use of Renewable Feedstocks
  8. Reduce Derivatives
  9. Catalysis
  10. Design for Degradation
  11. Real-time analysis for Pollution Prevention
  12. Safer Chemistry for Accident Prevention

Green Chemistry in Industry

Now that sustainability is on everybody’s top-of-mind, Green Chemistry is more important than ever. Just think about the amount of industries that rely on chemistry and whose activity has a great impact on the environment: pharma, agriculture, colorants, materials, consumer products… to name a few. 

This in part is due to the clear increase in awareness about environmental pollution. Especially since the last decades, people are becoming aware that we, as humans, are stressing the planet’s finite resources, and acknowledging that our consumption and waste have to go somewhere. And the current COVID crisis has consolidated this feeling. Just to mention some facts, there is fair evidence about:

If you watch the news, you might have noticed that some institutions are working non-stop to keep this issue present:

And special laws and regulations are being developed to promote more environmentally friendly, sustainable production processes and industries: REACH normative in European Union, ISO 14001, to name some of them.

In parallel, consumers are concerned about the impact the products they buy have in the environment and in their own bodies. Multiple initiatives inviting consumers to choose more “consciously” are nowadays on the front line, and they are demanding products that are respectful in the whole production chain: from manufacturing to recyclability. 

Having said all this, perhaps you are not very sure yet about the difference between green chemistry and general chemistry. The best way to describe it is that Green Chemistry’s main goal is to achieve the same or equivalent chemical reactions with a decrease in environmental damage.

And how is this accomplished?

Some techniques that are used for this aim include:

  • Catalysis: as mentioned in our first blog post, catalysis is the process of increasing a chemical reaction’s rate by the addition of an element denominated catalyst (like enzymes!), that is not consumed during the reaction and therefore can act repeatedly.
  • Synthetic biology: by applying engineering principles, the goal is to redesign and create new biological systems with the aim of providing novel solutions. Examples of this could be the creation of lab-grown meat, synthetic insulin or biofuels produced by algae.
  • Chemical synthesis: as the Nature journal definition says, chemical synthesis is “the process by which one or more chemical reactions are performed with the aim of converting a reactant or starting material into a product or multiple products”.

Why are industrial enzymes an example of Green Chemistry?

Maybe you are still wondering how green chemistry can help decrease pollution.

Like we mentioned earlier, Green Chemistry focuses on sustainability by looking for ways of preventing pollution, hazardous activity and resource waste. That’s why the use of industrial enzymes is such a sought-after solution for many companies who want to shift to greener production processes.

As biocatalysts, enzymes have a set of properties more beneficial than their non-enzymatic counterparts:

  • They are highly selective and specific, which allows chemists to have more control over their desired results.
  • They are effective under mild temperatures, which means significant energy savings.
  • They do not generate toxic waste.

As you can see, enzymes are pretty powerful! The main problem is adapting these enzymes to an industrial setting, which usually means tweaking the structure of an already existing enzyme to give it new features and make it work under certain conditions.That’s why at Zymvol we work to expand the use of green chemistry by creating custom-made enzymes for different industries. With some time and effort, we can make the world become a little bit greener.

 


References:

American Chemical Society. Green Chemistry History. https://www.acs.org/content/acs/en/greenchemistry/what-is-green-chemistry/history-of-green-chemistry.html 

CompoundChem (September 24, 2015). The Twelve Principles of Green Chemistry: What it is & Why it Matters. https://www.compoundchem.com/2015/09/24/green-chemistry/

Nature. Chemical Synthesis. https://www.nature.com/subjects/synthesis 

European Environment Agency (March 25, 2021) Synthetic biology and the environment. https://www.eea.europa.eu/publications/synthetic-biology-and-the-environment 

Aatresh, A.; Cumbers, J. (September 22, 2019) Can Synthetic Biology Make Insulin Faster, Better and Cheaper?. Synbiobeta. https://synbiobeta.com/can-synthetic-biology-make-insulin-faster-better-and-cheaper/ 

Straathof, A.J.J.; Adlercreutz, P. (2000). Applied Biocatalysis (2nd Ed.). CRC Press.


What are the Colors of Biotech?

Modern biotechnology arose in the late 20th century and is currently proving to be one of the key solutions to today’s problems, especially regarding health and the environment.

According to the UN Convention on Biological Diversity, Biotechnology is defined as any technical application that uses biological systems, living organisms or parts of them to make or modify products or processes with specific uses.

Giving that those products can be of many types, Biotechnology can cover a wide number of applications: from increasing the quality and resistance of farm crops, to keeping hospital patients healthy by keeping track of their vital signs -and, of course, engineering enzymes for industrial use.

The Colors of Biotech

As a way to structure this vast array of biotech possibilities, scientists started to categorize them by color. Each branch, a different color. That’s why you’ll often hear about the Rainbow Code of Biotechnology.

So what does each color represent in this biotech rainbow?

Blue Biotech

Focused on aquatic and marine fields.

Green Biotech

Agriculture. Focused on improving crops in an accurate, targeted way.

Red Biotech

Healthcare. Development of an advanced class of drugs and therapies.

Yellow Biotech

Food production.

Brown Biotech

Deserts and dry regions.

Golden Biotech

Bioinformatics, Computational Science, Agile organization and biological data analysis.

Gray Biotech

Environmental protection, maintenance of biodiversity and removal of pollutants.

White Biotech

Industrial processes and gene based tech. Use of enzymes and microorganisms to produce biobased products.

Purple Biotech

Laws, ethics and philosophy on biotechnology

Black Biotech

As you can imagine, black biotech focuses on a darker topic: Bioterrorism and biological warfare

At ZYMVOL we are part of the golden branch of biotechnology, since we use computational approaches to improve and enable the discovery of industrial enzymes. For that, we use technology based on computational molecular modeling, machine learning and other tools that allow us to fully understand and work with the chemical structure and interactions between enzyme, substrate and its environment.

We are golden, but our technology can help develop solutions in all other colors!

Modern biotechnology arose in the late 20th century and is currently proving to be one of the key solutions to today’s problems, especially regarding health and the environment.

According to the UN Convention on Biological Diversity, Biotechnology is defined as any technical application that uses biological systems, living organisms or parts of them to make or modify products or processes with specific uses.

Giving that those products can be of many types, Biotechnology can cover a wide number of applications: from increasing the quality and resistance of farm crops, to keeping hospital patients healthy by keeping track of their vital signs -and, of course, engineering enzymes for industrial use.

The Colors of Biotech

As a way to structure this vast array of biotech possibilities, scientists started to categorize them by color. Each branch, a different color. That’s why you’ll often hear about the Rainbow Code of Biotechnology.

So what does each color represent in this biotech rainbow?

  • Blue Biotech covers the aquatic and marine fields, by using ocean resources to create products and industrial applications.
  • Green Biotech has to do with everything agriculture-related, focused on improving crops in an accurate, targeted way.
  • Red Biotech centers on Healthcare, by developing an advanced class of drugs and therapies
  • Yellow Biotech covers Food Production
  • Brown Biotech for when Deserts and dry regions are involved
  • Golden Biotech is focused on the use of Bioinformatics, Computational Science, Agile organization and analysis of biological data. We recently wrote a post about what is Golden Biotech in more detail.
  • Gray Biotech encompasses the Environment and biodiversity, environmental protection, maintenance of biodiversity and removal of pollutants
  • White Biotech is for Industrial processes and gene based technologies, as well as the use of enzymes and microorganisms to produce biobased products
  • Purple Biotech is reserved for the laws, ethics and philosophy revolving around biotechnology
  • Black Biotech, as you can imagine, focuses on a darker topic: Bioterrorism and biological warfare

 

At ZYMVOL we are part of the golden branch of biotechnology, since we use computational approaches to improve and enable the discovery of industrial enzymes. For that, we use technology based on computational molecular modeling, machine learning and other tools that allow us to fully understand and work with the chemical structure and interactions between enzyme, substrate and its environment.

We are golden, but our technology can help develop solutions in all other colors!

Discover how we help our customers in Pharma, Chemicals, Biotech and other industries here.

 


References:

Convention on Biological Diversity (2006). Convention Text. Article 2. Use of Terms. https://www.cbd.int/convention/articles/?a=cbd-02

Kafarski, P. (2012). Rainbow Code of Biotechnology. CHEMIK. 66(8), 811-816.


Golden biotech: what it is and why it matters

You might be wondering: “what is golden biotech?”. The answer is rather simple: a biotechnology field that uses computer science as a main driving force. But do you know why it’s often referred to as “golden”? Or what exactly does it entail when taken into practice?

The color code of biotech

First of all, Golden biotech is known as “golden” because of the Rainbow Code of Biotechnology: a way to divide biotechnology’s vast array of applications into different categories, each one defined by a color.

Through this code, we know that when someone is talking about red biotech, they’re referring to health and medical applications; and when they’re talking about white biotech, they’re mostly talking about industrial uses.

All colors of the Biotech Rainbow are important, but what sets Golden Biotech apart is that it revolves around computers. For a technology to be considered golden, it has to rely heavily on some form of computational technique.

Golden biotech is a fairly recent addition to the biotech spectrum, but due to increasing advances in computer technology, one with a lot of potential to keep on growing in the following years.

Some of the main areas included in golden biotech are:

  • Bioinformatics. Field that focuses on analyzing large sets of biological data.
  • Nanotechnology. Field that uses technology at a nanoscale, or in other words, in atomic, molecular and macromolecular levels.
  • Computational Biology. Although closely linked to Bioinformatics, Computational Biology consists of using computational methods to develop models for the study of biological systems. This means relying on technologies like Machine Learning, Algorithms, Big Data (to name a few) for building these models.

Zymvol: an example of Golden Biotech company

Now that you know the definition of golden biotech and the main technologies behind it, you might say: “ok, but what does it really look like taken into practice?”

Just take a look at us. At ZYMVOL, we are golden. And is not that we are pretentious: it’s because we work in the golden branch of biotechnology.

At our company, we use a computational approach to improve and enable the discovery of industrial enzymes. We perform what we call “in silico enzyme evolution”, that is, engineer enzymes in the computer through molecular modeling, machine learning and other computer driven technologies. This allows us to fully understand the chemical structure and interactions between the enzyme, the substrate and their environment.

Take a look at the following video. What we do at ZYMVOL in a nutshell:

 

 

Through computer simulations we reproduce the enzyme, its environment and the desired reaction (substrates that interact with the enzyme) to be carried out: we perform different strategic mutations (amino acid substitutions) along the enzyme’s sequence and test its performance, looking at variables such as stability, activity or selectivity.

Thanks to computer simulations, we came up with the best combinations to test in the lab. We provide to our customers the sequences of the top performing candidates, so they produce in the lab only what matters.

This, at large, is the heart of golden biotechnology!

 


References:

Brown, K. (2018) Gold Biotechnology. Wikitech. https://wikitech21.wordpress.com/2018/08/26/gold-biotechnology/

DaSilva, Edgar J. (2004). The Colours of Biotechnology: Science, Development and Humankind. Electronic Journal of Biotechnology, 7(3), 01-02.

 


All you need to know about enzymes: biocatalysts for a greener future

If you’ve followed us for a while, you may already know that at ZYMVOL we work primarily with enzymes, designing and optimizing them through computer simulations. Enzymes are applied pretty much everywhere: from food products, cosmetics, in the synthesis of pharmaceutical products, and -as the natural biomolecules they are- even the inside of your own body.

But despite the key importance of these molecules in our daily lives, not many people know what they do! That’s why in this post we want to break down some of the main points regarding enzymes, its industrial uses and why they are the key to a greener, more sustainable chemical industry.

What are enzymes?

Enzymes are proteins naturally found in living organisms. They work as biocatalysts, which means they help “catalyze” or accelerate chemical processes. Instead of waiting hours or even days for the reaction to be completed, enzymes have the power to speed it up and produce many reactions in less than a second!

Take for example the lactase enzyme. When we drink milk, there’s a protein whose sole purpose is to break down lactose so we can digest it better. However, people who are lactose intolerant don’t have that enzyme, or simply  don’t have enough of it, so they have a harder time digesting it (and suffer the consequences of it).

What does an enzyme look like?

There are around 20 different types of amino acids in Nature, and they are crucial in defining an enzyme’s characteristics. An enzyme is made up of a sequence of amino acids, varying greatly on number. Some may just have 50 amino acids, some may have more than 200.

Here, the variability is enormous: proteins can have different lengths, and can be formed only by some of the around 20 available amino acids. That’s why In Nature, there are millions of different proteins, each one with a particular amino acid sequence.

Since they tend to fold into themselves, you’ll usually see images of enzymes represented like this.

However, the most important thing to know is that an enzyme’s amino acid sequence defines its shape. And its shape determines its function.

How does biocatalysis work?

As we mentioned previously, enzymes’ function is to catalyze chemical reactions. A catalyst is a molecule that increases the rate of a chemical reaction without being consumed by the reaction.

Enzymes catalyze all reactions that take place in living organisms, and these reactions can be of different types, like synthesis or degradation of products, among others.

To understand the process better, take a look at the following image, which represents the most accepted model of enzyme catalysis, the Induced Fit model, representing a synthesis reaction (formation of a product):

The enzyme-catalyzed reaction takes place in an inner region of the enzyme known as “active site”. The molecule that is bound in the active site is the “substrate”. Active sites are very specific, and only react with very specific types of “substrates”.

The “substrate” interacts with the “active site”, forming a transient “enzyme-substrate complex” that becomes an “enzyme-product complex” once the chemical changes take place.

Even if initially the substrate doesn’t adhere perfectly to the active site, the enzyme is flexible enough to adapt to the substrate. When the reaction finishes, the formed product is released and the free enzyme can bond to another substrate, starting the process again.

Examples of enzymes in our daily lives

As mentioned before, enzymes play a very important role by accelerating chemical reactions happening in our bodies, like breaking down lactose.

But this is just one example of the millions of possibilities that exist. Besides very technical uses, scientists have also applied these bio-molecules in the industry to create all kinds of products. Nowadays, they can be found in:

  • Pharmaceutical.
  • Chemical.
  • Food.
  • Animal Feed.
  • Cosmetics.
  • Cleaning.
  • Textile.
  • Recycling.
  • Pulp and paper products.
  • Flavors and Fragrances.

Industrial applications of enzymes

There’s a long history of enzymes being used to elaborate certain goods (for example, with alcohol fermentation) and, in the 20th century, they started to become more present in various industries. However, not all natural enzymes are valid for the overwhelming amount of different and highly specific chemical processes that take place in the current market.

Global trends on consumer needs and social change push companies to improve their products in different aspects, like  composition,  performance  or  manufacturing, while implementing sustainable production processes and reducing costs.

Therefore, protein engineering and enzyme improvement has gained popularity for companies who want to maintain their competitiveness, while also transforming their production to comply with green chemistry standards.

Some of the most popular industrial enzymes include:

  • Alcohol Dehydrogenases. Those that can reduce aldehydes into primary alcohols and ketones into secondary alcohols.
  • Oxidative Enzymes and Oxidoreductases. Those that cause or accelerate an oxidation reaction.
  • Lipases. Those that help disaggregate fat through hydrolysis.

Why enzymes are key for a sustainable future

There’s no denying that one of the biggest challenges the world faces nowadays is tackling climate change, which many environmental experts predict will have terrible consequences in the following decades. It’s no wonder that in 2015, the UN set a list of Sustainable Development Goals, with goals specifically focused on Climate related issues and Responsible Production.

What many people don’t know is that the use of enzymes in an industrial level can make a big difference in the way companies operate, and, therefore, have a significant and positive impact on the environment.

Why is that? Some advantages of using enzymes include:

Mild reaction conditions

Enzymes usually do not require harsh working conditions such as high temperatures or use of solvents or other hazardous auxiliary chemicals.

Eco-friendliness

Enzymes can substitute organic catalysts that require heavy metals that eventually are released to the environment.

Speed: enzymes are able to carry out chemical reactions in a extremely fast way

Efficiency: with proper reaction conditions, enzymes are able to process all present substrate and convert it into desired product

High product selectivity: enzymes are able to react with specific, targeted molecules, even in complex mixtures

Savings: with the advantages commented above, companies can save resources

Moreover, and according to the OECD, the potential of climate change mitigation coming from biotechnology processes and biobased products (in which improved enzymes applied to the chemical sector are included) “ranges from between 1 billion and 2.5 billion tons CO2 equivalent per year by 2030”.

Enzymes implemented as industrial biocatalysts are paving the way for a green chemistry revolution. As more industries start to embrace their use, we can get closer to reaching a true bioeconomy.


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If you’ve followed us for a while, you may already know that at ZYMVOL we work primarily with enzymes, designing and optimizing them through computer simulations. Enzymes are applied pretty much everywhere: from food products, cosmetics, in the synthesis of pharmaceutical products, and -as the natural biomolecules they are- even the inside of your own body.

But despite the key importance of these molecules in our daily lives, not many people know what they do! That’s why in this post we want to break down some of the main points regarding enzymes, its industrial uses and why they are the key to a greener, more sustainable chemical industry.

What are enzymes?

Enzymes are proteins naturally found in living organisms. They work as biocatalysts, which means they help “catalyze” or accelerate chemical processes. Instead of waiting hours or even days for the reaction to be completed, enzymes have the power to speed it up and produce many reactions in less than a second!

Take for example the lactase enzyme. When we drink milk, there’s a protein whose sole purpose is to break down lactose so we can digest it better. However, people who are lactose intolerant don’t have that enzyme, or simply  don’t have enough of it, so they have a harder time digesting it (and suffer the consequences of it).

What does an enzyme look like?

There are around 20 different types of amino acids in Nature, and they are crucial in defining an enzyme’s characteristics. An enzyme is made up of a sequence of amino acids, varying greatly on number. Some may just have 50 amino acids, some may have more than 200.

Here, the variability is enormous: proteins can have different lengths, and can be formed only by some of the around 20 available amino acids. That’s why In Nature, there are millions of different proteins, each one with a particular amino acid sequence.

Also, they tend to fold into themselves, that’s why you’ll usually see images of enzymes represented like this:

 

However, the most important thing to know is that an enzyme’s amino acid sequence defines its shape. And its shape determines its function.

How does biocatalysis work?

As we mentioned previously, enzymes’ function is to catalyze chemical reactions. A catalyst is a molecule that increases the rate of a chemical reaction without being consumed by the reaction.

Enzymes catalyze all reactions that take place in living organisms, and these reactions can be of different types, like synthesis or degradation of products, among others.

To understand the process better, take a look at the following image, which represents the most accepted model of enzyme catalysis, the Induced Fit model, representing a synthesis reaction (formation of a product):

The enzyme-catalyzed reaction takes place in an inner region of the enzyme known as “active site”. The molecule that is bound in the active site is the “substrate”. Active sites are very specific, and only react with very specific types of “substrates”.

The “substrate” interacts with the “active site”, forming a transient “enzyme-substrate complex” that becomes an “enzyme-product complex” once the chemical changes take place.

Even if initially the substrate doesn’t adhere perfectly to the active site, the enzyme is flexible enough to adapt to the substrate. When the reaction finishes, the formed product is released and the free enzyme can bond to another substrate, starting the process again.

Examples of enzymes in our daily lives

As mentioned before, enzymes play a very important role by accelerating chemical reactions happening in our bodies, like breaking down lactose.

But this is just one example of the millions of possibilities that exist. Besides very technical uses, scientists have also applied these bio-molecules in the industry to create all kinds of products. Nowadays, they can be found in:

  • Pharmaceutical.
  • Chemical.
  • Food.
  • Animal Feed.
  • Cosmetics.
  • Cleaning.
  • Textile.
  • Recycling.
  • Pulp and paper products.
  • Flavors and Fragrances.

Industrial applications of enzymes

There’s a long history of enzymes being used to elaborate certain goods (for example, with alcohol fermentation) and, in the 20th century, they started to become more present in various industries. However, not all natural enzymes are valid for the overwhelming amount of different and highly specific chemical processes that take place in the current market.

Global trends on consumer needs and social change push companies to improve their products in different aspects, like  composition,  performance  or  manufacturing, while implementing sustainable production processes and reducing costs.

Therefore, protein engineering and enzyme improvement has gained popularity for companies who want to maintain their competitiveness, while also transforming their production to comply with green chemistry standards.

Some of the most popular industrial enzymes include:

  • Alcohol Dehydrogenases. Those that can reduce aldehydes into primary alcohols and ketones into secondary alcohols.
  • Oxidative Enzymes and Oxidoreductases. Those that cause or accelerate an oxidation reaction.
  • Lipases. Those that help disaggregate fat through hydrolysis.

Why enzymes are key for a sustainable future

There’s no denying that one of the biggest challenges the world faces nowadays is tackling climate change, which many environmental experts predict will have terrible consequences in the following decades. It’s no wonder that in 2015, the UN set a list of Sustainable Development Goals, with goals specifically focused on Climate related issues and Responsible Production.

What many people don’t know is that the use of enzymes in an industrial level can make a big difference in the way companies operate, and, therefore, have a significant and positive impact on the environment.

Why is that? Some advantages of using enzymes include:

  • Mild reaction conditions: enzymes usually do not require harsh working conditions such as high temperatures or use of solvents or other hazardous auxiliary chemicals.
  • Eco-friendliness: enzymes can substitute organic catalysts that require heavy metals that eventually are released to the environment.
  • Speed: enzymes are able to carry out chemical reactions in a extremely fast way
  • Efficiency: with proper reaction conditions, enzymes are able to process all present substrate and convert it into desired product
  • High product selectivity: enzymes are able to react with specific, targeted molecules, even in complex mixtures
  • Savings: with the advantages commented above, companies can save resources

Moreover, and according to the OECD, the potential of climate change mitigation coming from biotechnology processes and biobased products (in which improved enzymes applied to the chemical sector are included) “ranges from between 1 billion and 2.5 billion tons CO2 equivalent per year by 2030”.

Enzymes implemented as industrial biocatalysts are paving the way for a green chemistry revolution. As more industries start to embrace their use, we can get closer to reaching a true bioeconomy.

 


References:

Heckmann, C. M.; Paradisi, F. (2020). Looking Back: A Short History of the Discovery of Enzymes and How They Became Powerful Chemical Tools. ChemCatChem, 12(24), 6082-6102.

Lehninger Principles of Biochemistry, 5th Edition. D.L Nelson and M.M Cox (2008)

Neitzel, J. J. (2010) Enzyme Catalysis: The Serine Proteases . Nature Education 3(9):21

Nature Education eBooks chapters Essentials of Cell Biology, Unit 2.4 and Cell Biology for Seminars, Unit 2.4  © 2014 Nature Education https://www.nature.com/scitable/topicpage/protein-structure-14122136/

OECD.(2011). Industrial Biotechnology and Climate Change. Opportunities and Challenges. http://www.oecd.org/science/emerging-tech/49024032.pdf

Phillips, Rob; Milo, Ron; How many reactions do enzymes carry out each second? Cell Biology by the Numbers. http://book.bionumbers.org/how-many-reactions-do-enzymes-carry-out-each-second/