enzyme development services

Enzymes are crucial biochemical tools for the catalysis of various commercially significant processes, including the manufacture of new therapeutics, diagnostics, food and textile processing and cleaning products. They have been used for many years, for example, in the manufacture of beer, cheese, wine and textiles such as leather. 

Following the rapid reduction of the cost of DNA synthesis and the increase in the availability of genome sequences, and therefore enzyme sequences, modern biotechnology now allows rapid and cost-effective access to much more active and specific enzymes. These enzyme development services can help companies access new products, improve sustainability and efficiency and/or reduce the cost of existing processes. 

Proteins have a variety of uses in addition to enzymatic activity, such as in vaccines, textiles, food and personal care (e.g. cosmetics) or as therapeutics.

Enzyme discovery and the efficient and scalable production of proteins and enzymes via microbial fermentation are cornerstones of industrial biotechnology - we can support all of this with our enzyme development services. 

The team at Isomerase have extensive experience with designing, discovering and producing new or existing enzymes or proteins, developing enzyme-based processes, and products and developing routes toward scalable and cost-effective protein fermentation.

How can Isomerase help you with enzyme development services and protein research and development?

Isomerase has supplied protein and enzyme development services to partners on many projects where the final product is a protein, including many functional enzymes. These projects can involve various stages:

  • Bioinformatics guided enzyme ID - where an activity in a microbial strain is known, but not the actual gene coding for the enzyme of interest we can carry out a process of enzyme discovery using our well-established biotechnology processes.
  • Enzyme engineering - we can manipulate the activity of a known enzyme using techniques such as directed evolution and structure-guided engineering
  • Enzyme expression - following the selection of an enzyme, we can then generate expression strains and use high-density fermentation protocols along with associated downstream processing (DSP) to help prepare the strain and process for scale-up
  • Enzyme supply - we can generate initial material for testing and then support with tech transfer to a CDMO with the desired scale-up capabilities and location.

Why choose Isomerase for enzyme development services and discovery and development of proteins and enzymes?

The team at Isomerase can carry out a wide range of enzyme development services and support all steps of the process to generate enzymes or proteins for industry. From enzyme discovery and enzyme engineering, expression and isolation of enzymes and proteins all the way through to the development of protein fermentation processes and downstream processing, supply of material and tech transfer to the scale required and eventual scaleup. We also work with a wide range of industrial expression hosts, including the standard Escherichia coli BL21 (DE3) through to the eukaryotic Pichia pastoris (Komagataella phaffi) and Saccharomyces cerevisiae along with less commonly used hosts, such as Streptomyces. 

Our experience working with partners across a range of industrial sectors means we are specialised in selecting the optimal process for you depending on your solubility, toxicity, secretion and processing requirements. Our pilot scale plant is set up to perform your protein fermentation at the development scale.

At Isomerase, our approach to enzyme manufacturing is designed to provide you with a wide range of options and ensure the success of your project. We understand that choosing the right host strain is crucial, and that's why we offer a variety of proprietary bacterial and fungal hosts. Whether working with Escherichia coli, Pichia pastoris or another microbial strain, our goal is to help you identify the enzyme sequence encoding the activity of interest and the best strain and process to express and isolate it effectively. Our experienced team will guide you through the process, providing support in engineering and optimizing the production (USP and DSP) process. By leveraging the power of microbial strains, we enable scalable production of your desired product or the isolation of the enzyme for cell-free biocatalytic processes. Rest assured that with Isomerase, you'll have access to a diverse range of host strains and the expertise to choose the right one for your specific project.

We would love to discuss your project and explore how we can support you with our enzyme development services – please contact us.

Examples of proteins

There are around 20,000 protein-coding genes in the human genome alone, producing over 100,000 different proteins. Once we take into account the vast number of other sequenced eukaryotic and prokaryotic genomes, the total number of sequenced protein sequences becomes vast. Almost all of these proteins are potential targets for a wide variety of applications. 

Proteins can be classified in a number of ways, including by structure, function or chemistry.

The structural classification includes grouping proteins into classes such as globular (e.g. albumin, haemoglobin, myoglobin and insulin), fibrous (e.g. collagen or keratin) and membrane proteins (e.g. G protein-coupled receptors (GPCRs), integrins and glucose permease.

Functional classification groups proteins by function, such as structural proteins (e.g. actin, keratin and collagen), enzymes (see below), transport proteins (such as albumin, myoglobin and haemoglobin), hormones (such as testosterone, insulin and somatotropin (hGH)), immunoglobulins (antibodies), receptors (such as GPCRs and ion channels), adhesion proteins (such as integrins, cadherins and selectins) and storage proteins (such as ovalbumin, globulins, casein and prolamins such as zein).

Examples of enzymes

Below is a non-exhaustive list of example enzymes (grouped by class) potentially suitable for Isomerase's enzyme development services, enzyme engineering and enzyme fermentation.

Enzymes are typically classified according to function using the International Union of Biochemistry and Molecular Biology (IUBMB) system as follows:

Class 1 (EC 1): Oxidoreductases – these catalyze oxidation-reduction reactions where electrons are transferred between molecules. Subclasses are classified according to what they act upon.

 

  • EC 1.1 – CH-OH donors including alcohol oxidoreductases such as methanol dehydrogenase
  • EC 1.2 – Aldehyde or oxo donors such as aldehyde dehydrogenase and pyruvate dehydrogenase
  • EC 1.3 – CH-CH donors such as fumarate reductase and succinate dehydrogenase
  • EC 1.4 – CH-NH2 donors such as alanine dehydrogenase and monoamine oxidase
  • EC 1.5 – CH-NH donors such as Dihydrofolate reductase and FMN reductase
  • EC 1.6 – NADH or NADPH such as NADPH: quinone reductase and Cytochrome P450 BM3
  • EC 1.7 – Other nitrogenous donors such as GMP reductase and nitrate reductase
  • EC 1.8 – Sulfur donors such as Glutathione reductase and Thioredoxin reductase
  • EC 1.9 – Heme donors such as cytochrome C oxidase
  • EC 1.10 – Diphenol donors such as catechol oxidase and laccase
  • EC 1.11 – Peroxidases such as catalase and haloperoxidase
  • EC 1.12 – Hydrogen donors such as hydrogen dehydrogenase
  • EC 1.13 – Oxygenases such as catechol 1,2 dioxygenase, lipooxygenase and lactate 2- monooxygenase
  • EC 1.14 – Molecular oxygen incorporation including Cytochrome P450 enzymes such as CYP3A4, CYP2D6 and other monooxygenases such as ketosteroid monooxygenase and  erythromycin 12-hydroxylase
  • EC 1.15 – Superoxide radical acceptors such as superoxide dismutase
  • EC 1.16 – Metal ion oxidisers such as diferric-transferrin reductase
  • EC 1.17 – CH or CH2 groups such as formate dehydrogenase
  • EC 1.18 – Iron-sulfur donors such as ferredoxin—NAD(+) reductase
  • EC 1.19 - Reduced flavodixin donors such as nitrogenase
  • EC 1.20 – Phosphorus or arsenic donors such as mycoredoxin and glutaredoxin
  • EC 1.21 – Act on X-H and Y-H to form X-Y such as isopenicillin N synthase and sarcosine reductase

Class 2 (EC 2): Transferases – catalyze the transfer of functional groups, such as acetyl, phosphate or amino groups from one molecule to another. Subclass examples include:

  • EC 2.1 – Methyltransferases and formyltransferases
  • EC 2.2 – Transketolases and transaldolases
  • EC 2.3 – Acyltransferases
  • EC 2.4 - Glycosyltransferases
  • EC 2.5 – Chlorophyll synthase and riboflavin synthase
  • EC 2.6 – Transaminases
  • EC 2.7 – Phosphotransferases, polymerases and kinases
  • EC 2.8 – Sulfurtransferases and sulfotransferases
  • EC 2.9 – Selenotransferases
  • EC 2.10 – Molybdenumtransferases and Tungstentransferases

Class 3 (EC 3): Hydrolases – catalyze bond hydrolysis, such as where water molecules are used to break a chemical bond. Subclasses are categorized according to the bonds they act upon:

  • EC 3.1 – Esterases such as nucleases, lipases and phosphatases
  • EC 3.2 – Sugars such as DNA glcosylases and nucleosidases
  • EC 3.3 – Ether bonds such as epoxide hydrolase and isochorismatase
  • EC 3.4 – Peptide bonds such as proteases and peptidases
  • EC 3.5 – Non-peptidic carbon-nitrogen bonds such as aminohydrolases and histone deacetylases
  • EC 3.6 – Acid anhydrides such as helicases and diphosphatases
  • EC 3.7 – Carbon-carbon bonds such as kynureninase
  • EC 3.8 – Halide bonds such as haloalkane dehalogenase
  • EC 3.9 – Phosphorus-nitrogen bonds such as phosphoamidase
  • EC 3.10 - Sulfur-nitrogen bonds such as cyclamate sulfohydrolase
  • EC 3.11 - Carbon-phosphorus bonds such as phosphonopyruvate hydrolase
  • EC 3.12 – Sulfur-sulfur bonds such as trithionate hydrolase
  • EC 3.13 – Carbon-sulfur bonds such as carbonyl sulfide hydrolase

Class 4 (EC 4): Lyases – catalyze elimination of chemical bonds by means other than hydrolysis and oxidation. Subclass examples include:

  • EC 4.1 – Decarboxylases and Aldehyde lyases
  • EC 4.2 – Dehydratases
  • EC 4.3 – Ammonia lyases and cyclodeaminases
  • EC 4.4 – Desulfhydrases and sulfolyases
  • EC 4.5 – Dehalogenases such as dechlorinases
  • EC 4.6 – Adenylate cyclase and guanylyl cyclase
  • EC 4.99 / EC 4.98 – Ferrochelatase and heme ligase

Class 5 (EC 5): Isomerases – convert a molecule from one isomer to another. Subclass examples include:

  • EC 5.1 – Racemases and epimerases, such as methionine racemase
  • EC 5.2 – Cis-trans isomerases such as maleate isomerase
  • EC 5.3 – Intramolecular oxidases such as Protein disulfide isomerase and phenylpyruvate isomerase
  • EC 5.4 – Intramolecular transferases such as Mutases and isochorismate synthase
  • EC 5.5 – Intramolecular lyases such as Cycloisomerases

Class 6 (EC 6): Ligases – catalyze ligation of two molecules via a chemical bond, typically resulting in new C-O, C-S or C-N bonds. Subclass examples include:

  • EC 6.2 – Carbon-oxygen bond formers such as tRNA ligases
  • EC 6.2 – Carbon-sulfur bond formers such as CoA ligases or CoA synthases
  • EC 6.3 – Carbon-nitrogen bond formers such as NAD+ synthase, glutathione synthetase and D-alanine-D-alanine ligase
  • EC 6.4 – Carbon-carbon bond formers such as acetyl CoA carboxylase or pyruvate carboxylase
  • EC 6.5 – Phosphoric ester bond formers such as DNA ligase and RNA ligase
  • EC 6.6 – Nitrogen-metal bond formers such as chelatases

Class 7 (EC 7): Translocases – covers enzymes assisting in moving another molecule, usually across a membrane. Subclass examples include:

  • EC 7.1 – Catalyzes translocation of hydrons, such as cyctochrome-C oxidase
  • EC 7.2 - Catalyzes translocation of inorganic cations and chelates, such as
  • EC 7.3 - Catalyzes translocation of inorganic anions, such as ABC-type phosphate transporters and ABC-type sulfate transporters
  • EC 7.4 - Catalyzes translocation of amino acids and peptides, such as ABC-type oligopeptide transporters and ABC-type protein transporters
  • EC 7.5 - Catalyzes translocation of carbohydrates and derivatives such as ABC-type maltose transporter and ABC-type oligosaccharide transporter
  • EC 7.6 – Catalyzes translocation of other compounds, such as ABC-type heme transporter

Contact us today about our enzyme development services

Get in touch via our contact us page about our enzyme development services.

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