Biocatalysis Solutions: Biocatalysts are essential tools in chemical synthesis, particularly in the synthesis of pharmaceutical and fine chemical targets. As highly selective catalysts, they offer a direct and simple way to synthesise complex achiral and chiral compounds. The application of biocatalysts in the pharmaceutical and fine chemical industries continues to grow as it moves from the domain of specialised technology to mainstream methodology. This movement has been facilitated by the increasing commercial ‘off-the-shelf’ availability of biocatalysts. Almac has heavily invested in this area to secure the supply of selectAZymeTM biocatalysts for clients’ non-GMP and GMP manufacturing projects.
Our Biocatalysis Group
Consisting of computational, molecular and micro biologists, enzymologists, organic chemists and analysts, the group has demonstrated expertise in gene identification, expression, enzyme evolution, fermentation, enzyme production and biotransformation scale-up. Expertise ranges from enzyme production to the synthesis of complex chiral APIs from mg-tonne scale.
Our team is closely linked to the process chemistry and manufacturing chemistry groups, where enzyme discovery and development is integrated with screening and route definition. Each member of the team brings expertise to complex processes procedures and can rapidly implement an enzymatic process to significantly improve the yield and timelines of a multi-step synthesis.
This exclusive technology platform consists of a number of recombinant enzyme panels that can be used in chemical processing across multiple functional group interchanges.
With this unique selectAZymeTM platform, we can offer you a range of enzymes suitable for carrying out a wide variety of chemical reactions. We have the expertise to guide your biosynthesis from conception to scale-up.
We can deliver the following:
- FTE or FFS contracts
- Screening of our biocatalyst toolbox with customer substrates – comprising of biocatalyst selection and route demonstration
- Biocatalytic route invention and process development
- Enzyme supply on a £ / Kg basis
- Enzyme development and evolution
- Tech transfer and ongoing support through all the manufacturing steps, including the training of personnel, if required
- Supply of chiral intermediates
- Microbial screening and molecular biology for the development of novel biocatalysts
- Fermentation development and scale-up
- Metabolite synthesis
Enzyme Panel Quotation Request
Biotransformation Process Development
Enzyme Panel Quotation Request
Almac offers a range of biocatalysts in easy to use kits for rapid customer evaluation without any IP issues. Development and manufacturing quantities are available on a transparent and simple £/kg basis.
Submit the quotation request form above and a confirmation email will be sent within 48 hours of receipt.
For further enquires involving biocatalysis, chiral chemistry or bulk ordering of biocatalysts please contact us at firstname.lastname@example.org.
Click here to download Almac’s Terms & Conditions.
Making Biocatalysts Available To You Through Our Platform Of Enzyme Panels
Our dedicated biocatalysis group provides an in- house screening facility using our selectAZymeTM panels and subsequent identification of a suitably active and selective enzyme for your transformation. In addition, the group can build enzyme panels for your transformation, through gene selection, gene synthesis and cloning followed by expression and delivery of enzyme for screening.
Typical Screening Projects Involve:
- High throughput screening development and implementation
- Assay development
- UPLC / HPLC method development and analysis
- Selection of the desired enzymes for your transformation
Enzyme Panel Building
Using bioinformatics, gene identification, cloning and expression techniques Almac can build enzyme panels for you. Our expertise covers:
- Gene identification and mutation selection
- Cloning and expression
- Enzyme fermentation and delivery of easy-to-use enzyme for chemical transformation
Almac has a large collection of microbes that are used in bioprocessing; from metabolite synthesis through to large scale processing. Our expertise covers:
- Strain maintenance and collection
- Wild type screening, mutation and the identification of microbial hit systems
- Microbial fermentation expertise
- Microbial bioprocessing expertise
Biotransformation Process Development
Biocatalysis: An Efficient Processing Solution? We Think So!
There is a common misconception that enzymes are unstable and expensive, work only under high dilution, and do not lend themselves well to scalable chemical processing. However, there are ever-increasing numbers of biotransformations being performed at a multi-tonne manufacturing scale, where biocatalysis has provided the most efficient processing solution. In addition, the timelines required to develop these bioprocesses are now comparable with chemistry scale-up, due to the availability of “off-the-shelf” enzymes, such as those in our selectAZymeTM platform.
There are a number of key factors involved in the development of a biocatalytic process such as substrate concentration, enzyme loading, solvent choice, product extraction and isolation. Development work consists of investigating reaction robustness by stress testing each of the relevant parameters, taking the reaction to its limits and then setting the optimised conditions.
We have carried out bioprocesses to GMP standard in our manufacturing plant and tech transferred processes to our customers from mg to tonne manufacture.
Process Development of Biotransformations
We have extensive experience in biotransformation process development:
- Process development expertise in bioprocessing for scale-up including hydrolase, ketoreductase, transaminase, BVMO, nitrile hydrates, nitrilase, P450 and cyanide dihydratase enzymes.
- Development of bioprocesses using carousels for reaction optimisation with DOE software.
- Qualitative and quantitative analysis and identification by NMR, HPLC, LCMS, with ability for further analytical support when required (including, protein, protein fragment, endotoxin and cell debris analysis).
- Freeze drying and spray drying expertise for accessing formulated enzymes.
- Immobilisation of selected enzymes on to various supports such as resins and chitin to improve cost contribution of enzyme and minimise work up operations.
- Rapid column screening and selection for both chiral and achiral methods (GC / HPLC).
- High throughput screening of enzymes using HPLC with 96 well plate holders.
- Isolation and purification of compounds using Biotage, Prep LC (chiral phase / achiral (reverse phase C18).
- Development of alternative processes to batch reactions such as continuous processing (plug reactors / continuous flow).
Almac has expertise in immobilisation screening and scale-up of immobilised catalysts, as well as whole cell and isolated enzyme immobilisation. Our immobilisation techniques cover:
- Binding to a prefabricated support (carrier)
- Entrapment in organic or inorganic polymer matrices
- Cross-linking of enzyme molecules
- Application of immobilised enzyme under continuous flow processing
Providing the Tech Support Necessary for the Production of Viable Enzymes
We have an integrated Molecular Biology facility that provides all of the technical support and expertise you need to produce commercially viable enzymes.
Our facility can provide biocatalysts in any form you desire, whether it be cloned DNA in a plasmid of choice or large quantities of purified protein. We recognise that your needs are as unique as your fingerprints, so we provide you with a tailored biocatalysis solution. Novel biocatalysts can be sourced from our own cDNA libraries and enhanced through mutagenesis, providing you with a custom biocatalyst.
Enzyme performance can be increased through computational and directed evolution expertise. Enzymes have been evolved for increased selectivity, activity, solvent tolerance, and thermostability.
Computational Biology Capabilities
Our expertise in computational biology and bioinformatics includes:
- Access to large databases of gene and protein sequences
- A wide range of DNA, genomic and protein sequence analytical tools, as well as, evolutionary biology computational tools
- Available resource for building, annotating, and querying biological pathways
- We can offer a comprehensive study of the protein structure and function utilizing 3-D protein modeling software tools
- Highly qualified bioinformaticians who provide inclusive analysis on DNA, protein, and protein modelling
Our expertise in enzyme evolution and engineering includes:
- The capability to perform directed evolution by both site-specific and random mutagenesis
- Expertise in a number of different expression systems, such as E.coli, Pichia, Steptomycetes and Aspergillus
- Bioinformatic expertise that allows us to perform saturation mutagenesis, a powerful tool in the field of directed evolution
- Use of a colony picker, which will automatically screen a large selection of colonies present on the solid media and pick the colonies that require further testing
- Parallel UPLC systems for rapid screening of libraries to show either activity or selectivity of the enzyme
- A liquid handler for the automated process of dispensing chemical or biological reagents, providing accuracy and ease for a large number of samples
- High throughput screening may be carried out in a 96 well format using a colorimetric assay, HPLC or MS analysis
- Access to a novel system that allows the glycosylation of proteins in E.coli
We have extensive experience in fermentation development and scale-up. We have a dedicated team who have handled a broad spectrum of microorganisms including recombinant and wild type strains for the production of enzymes and bioproducts at large scale.
We offer customer specific enzymes such as: concentrated biomass (cell paste), enzyme concentrate as a cell free extract, lyophilised enzyme powder or immobilised enzyme
Our expertise in enzyme evolution and engineering includes:
- Fermentation development and scale-up from 1 L to 63 m3 to deliver biocatalyst as cell paste, liquid, spray dried or lyophilised enzyme.
- Parallel fermentation development to define process parameters including down-stream processing
- Design of experiment software for rapid development
- Enzyme activity testing and enzyme immobilisation
Metabolite synthesis is another tool within selectAZyme’sTM service offering that provides access to both oxidative and glycosylated products. Almac has implemented state-of-the-art biocatalytic technology for rapid metabolite synthesis, isolation and structural identification.
We have developed both recombinant and microbial P450 technology to access metabolites from mg to 100s grams scale. These enzymes, which mimic human P450 systems, are a powerful tool for accessing difficult to synthesise metabolites rapidly.
- Cloned Human P450
- Cloned Microbial P450
- Extensive microbial collection
Metabolite Isolation/Structure ID
- Analytical and prep LC
- High-field NMR
Almac’s scale-up ability allows us to rapidly take ‘hits’ from conception to gram delivery as and when our customers require the products.
In addition, Almac can also supply radiolabelled metabolites utilising our in-house isotope chemistry group.
Our Easy-to-use Kits Allow For Rapid Customer Evaluation
We offer a range of biocatalysts in easy-to-use kits. These allow for rapid customer evaluation without any IP issues. Development and manufacturing quantities are available on a transparent and simple £/ kg basis.
Our exclusive selectAZymeTM platform consists of a range of enzyme libraries which are commercially available as a series of kits. These include:
Hydrolase Enzyme Screening Kit (HESK-4800)
(48 enzymes for selective hydrolysis in aqueous media, selective acylation in non-aqueous media, resolution of secondary alcohols, amines and thiols, formation of peptides)
Carbonyl Reductase Enzyme Screening Kit (CESK-6000)
60 enzymes for the synthesis of enantiomerically pure (R) and (S) chiral alcohols by enzymatic reduction of ketone
Aldehyde Reductase Enzyme Screening Kit (AESK-1600)
16 enzymes for the synthesis of primary alcohols by enzymatic reduction of aldehydes, selective reduction of an aldehyde in the presence of a ketone
Transaminase Enzyme Screening Kit (TESK-3600)
36 enzymes for the synthesis of enantiomerically pure (R) and (S) chiral amines by either resolution or by asymmetric synthesis
Nitrile Manipulator Enzyme Screening Kit (NESK-2400)
24 enzymes for the synthesis of amides and carboxylic acids by enzymatic hydrolysis of nitriles. Consists of 15 nitrilase enzymes and 9 nitrile hydratase enzymes
Epoxide Hydrolase Enzyme Screening Kit (EHESK-500)
5 enzymes for the resolution of racemic epoxides by selective ring opening in aqueous media resulting in optically active anti diols and epoxides
Phenylalanine Dehydrogenase Enzyme Screening Kit (PDESK-500)
5 enzymes for the synthesis of L-amino acids by reductive amination of 2-oxo acids
P450 Monooxygenase Enzyme Screening Kit (OxESK-2000)
20 enzymes for the selective oxidation of unactivated carbons to produce alcohols and phenols, selective epoxidation of olefins, N- and O-dealkylations
Ene Reductase Enzyme Screening Kit (ERESK-2300)
23 enzymes for the reduction of electron deficient olefins. Allow formation of up to two new chiral centers from pro-chiral olefins. Allows regioselective reduction in a molecule containing more than one alkene moiety
Hyperactivated Hydrolase Enzyme Screening Kit (HAHESK-1000)
10 hyperactivated hydrolase enzymes
Other enzymes available include:
Lactamases, Amine Oxidases, Glucose Dehydrogenase (GDH), Lactate Dehydrogenase (LDH), Dihydrofolate Reductase (DHFR), Aspartate ammonia lyase, Cyanide Dihydratases, Hydroxy nitrile lyase and many more.
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