Even modest improvements using our protein and enzyme development services can have drastic impacts on the quality and manufacturing cost of end products.
Industrial enzymes
Applications
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. For example, they have been used for millennia in the manufacture of beer, cheese, wine, and textiles such as leather.Commercialisation using our enzyme development services
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 as a whole
Outwith enzymatic activity, proteins have a variety of applications, such as in vaccines, textiles, food, personal care (e.g., cosmetics), and therapeutics. Most of our techniques and technologies have been designed for optimisation not only of enzymes but also of non-catalytic proteins.
Our expertise
We have extensive experience designing, discovering, and producing new or existing enzymes and proteins. This includes developing enzyme-based processes and products whilst developing routes toward scalable and cost-effective protein fermentation.
How do our enzyme development services and protein R&D help you?
We provide protein and enzyme development services to partners on many projects involving various stages:
- EvoSelect®: We have developed an in-house machine learning tool for enzyme engineering, which can take a native sequence and generate variants based on evolutionary couplings. The generated variant sequences exhibit low sequence identity to parent templates, exhibit enhanced thermal and solvent stability, whilst supporting the development of novel, patentable innovations.
- 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 generate expression strains and use high-density fermentation protocols along with associated downstream processing (DSP) to help prepare for scale-up.
- Enzyme supply: We can generate initial material for testing and support with tech transfer to a CDMO with the desired scale-up capabilities and location.
Why choose Isomerase for protein and enzyme development services?
We can carry out a wide range of enzyme development services and support all steps of the process to generate industrial enzymes or proteins. We also work with a wide range of industrial expression hosts, including the standard Escherichia coli BL21 (DE3), eukaryotic Pichia pastoris (Komagataella phaffi), Saccharomyces cerevisiae, and less commonly used hosts, such as Streptomyces.
Variety of sectors and scales
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.
End-to-end enzyme development services
We designed our enzyme engineering approach 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 with 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 the scalable production of your desired product or the isolation of the enzyme for cell-free biocatalytic processes. You will have access to a diverse range of host strains and the expertise to choose the right one for your specific project.
To discuss your project and explore how we can support you with our enzyme development services, contact us.
Examples
Proteins
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).
Enzymes
Below is a non-exhaustive list of example enzymes (grouped by class) which are 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
Catalyse bond hydrolysis, such as where water molecules are used to break a chemical bond. Subclasses are categorised 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
Catalyse 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
Catalyse 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 – Catalyses translocation of hydrons, such as cyctochrome-C oxidase
- EC 7.2 - Catalyses translocation of inorganic cations and chelates, such as
- EC 7.3 - Catalyses translocation of inorganic anions, such as ABC-type phosphate transporters and ABC-type sulfate transporters
- EC 7.4 - Catalyses translocation of amino acids and peptides, such as ABC-type oligopeptide transporters and ABC-type protein transporters
- EC 7.5 - Catalyses translocation of carbohydrates and derivatives such as ABC-type maltose transporter and ABC-type oligosaccharide transporter
- EC 7.6 – Catalyses translocation of other compounds, such as ABC-type heme transporter