Biocatalytic Process Development
Biocatalytic Process Development for Scalable, Selective Routes
We develop enzyme- and whole-cell-catalyzed transformations from concept to a scalable, cost-efficient manufacturing route.
What Biocatalytic Process Development Is
Biocatalytic process development turns an enzyme-catalyzed transformation into a robust, reproducible manufacturing route. It spans enzyme discovery and engineering, biocatalyst production by fermentation or expression, reaction screening and optimization, cofactor or co-substrate regeneration strategy, and scale-up in stirred-tank bioreactors through downstream processing and purification.
The work matters because enzymes offer regio-, chemo-, and stereo-selectivity that is difficult to match with conventional chemistry, often reducing protecting-group steps and side-product formation. The central engineering constraints are cofactor dependence and co-substrate cost, which is why whole-cell systems or in situ cofactor regeneration are commonly used to keep a route economically viable at scale.
Selective Transformations
Enzymes are highly selective catalysts with strong functional-group tolerance, which can minimize wasteful protecting-group chemistry and side-product formation.
- Regio-, chemo-, and stereoselective catalysis
- Cascade or one-pot multistep transformations
- Mild aqueous conditions with water as the major solvent
Cofactor and Co-Substrate Strategy
Many oxidoreductases and transferases depend on stoichiometric cofactors or expensive co-substrates, so regeneration strategy is designed into the route from the start.
- Whole-cell systems for cofactor-dependent enzymes
- In situ cofactor or co-substrate regeneration
- Substrate loading and co-solvent compatibility assessed early
From Bench to Bioreactor
Reaction conditions, biocatalyst format, and isolation procedures are developed together so the route remains workable as it moves toward larger stirred-tank and continuous formats.
- Biocatalyst production by fermentation or expression
- Immobilized enzyme or whole-cell process formats
- Downstream purification and process analytics
| Strain sourcing, genome sequencing and analysis, enzyme shortlisting, library screening, and property improvement are combined to confirm activity and refine the biocatalyst. | |||
| Expression in microbial hosts and fermentation, through cell lysis and purification | |||
| Reaction screening, validated analytical tools, and multivariate Design of Experiments campaigns are used to locate robust operating conditions. | |||
| Stirred-tank bioreactor operation, fed-batch or continuous formats, and immobilized or whole-cell process design are evaluated to define a scalable route. |
How an Engagement Works
Engagements follow a staged path from target definition to a documented, transferable process. Each stage produces defined outputs that feed the next, so decisions are made on data rather than assumption.
Target and Route Definition
We review the target transformation, substrate, and manufacturing intent, then agree the biocatalyst format, analytical needs, and the scope of the development program.
Enzyme Discovery and Engineering
Strains are sourced and genomes sequenced and analyzed to generate enzyme shortlists, and libraries are screened to confirm activity before properties are improved as needed.
Biocatalyst Production
The selected enzyme is expressed in a suitable microbial host and produced by fermentation, followed by cell lysis and purification to deliver the biocatalyst in the required format.
Reaction and Process Optimization
Reaction conditions, substrate loading, co-solvent compatibility, and cofactor or co-substrate regeneration are optimized using validated analytics and multivariate Design of Experiments.
Where We Add Differentiation
The value of a biocatalytic route is realized when selectivity, cofactor economics, and isolation are solved together rather than in isolation. Our development work is organized around that integration.
Because biocatalysis is applied case by case, we tailor the program to the specific enzyme class, substrate, and scale target instead of applying a single fixed template.
One Route, Not Isolated Steps
Enzyme engineering, biocatalyst production, reaction optimization, and isolation are developed as a connected route so improvements in one stage are not lost in another.
- Biocatalyst format chosen for the commercial process
- Reaction and isolation developed in parallel
- Process documentation generated for transfer
Regeneration Designed In
Cofactor dependence and co-substrate cost are treated as central design constraints, with whole-cell systems or in situ regeneration evaluated as part of the route.
- Whole-cell options for cofactor-dependent enzymes
- Regeneration strategy assessed at reaction screening
- Substrate loading balanced against inhibition
Free, Immobilized, or Whole-Cell
Enzyme format is matched to the process, including immobilized preparations and continuous-flow formats where they suit the transformation and scale target.
- Immobilized enzyme and whole-cell process design
- Stirred-tank and continuous-flow formats considered
- Isolation procedures adapted to biocatalysis
Service Scope
Scope is defined case by case after consultation. The table below describes the parameters that are typically customized and how they are handled, rather than presenting fixed packages.
Final scope, screening depth, analytical coverage, and validation depth are agreed in the project SOW.
| Parameter | Typical project scope | How it is set | Notes |
|---|---|---|---|
| Target transformation | Enzyme- or whole-cell-catalyzed reaction defined by the client's route | Agreed at project definition | Substrate and product specifications confirmed first |
| Enzyme sourcing and engineering | Strain sourcing, genome analysis, enzyme shortlisting, and library screening | Scoped to the starting point of the program | Property improvement included when needed |
| Biocatalyst production | Expression host selection, fermentation, lysis, and purification | Host and format selected for the enzyme | Semi-pure or purified enzyme as required |
| Reaction optimization | Conditions, substrate loading, co-solvent, and cofactor regeneration | Design of Experiments campaigns as scoped | Validated analytical tools used throughout |
| Process format | Free enzyme, immobilized enzyme, or whole-cell system | Selected against the scale target | Stirred-tank and continuous-flow options |
| Downstream and analytics | Isolation procedure development, purification, and process analytics | Scoped to product and purity needs | Documentation prepared for transfer |
Deliverables and Documentation
Deliverables are defined in the project SOW and typically include the biocatalyst, the optimized process description, and the analytical and documentation package needed to move the route forward.
Where a compound supply is requested, the full biocatalysis workflow can be carried out and the product supplied with a Certificate of Analysis.
| Deliverable | Description | Format | Notes |
|---|---|---|---|
| Biocatalyst | Enzyme or whole-cell biocatalyst produced for the project | Semi-pure or purified preparation | Quantity scoped per project |
| Optimized process | Reaction conditions, substrate loading, and regeneration strategy | Written process description | Includes scale-up parameters as scoped |
| Analytical package | Validated analytical methods and reaction data | Data package | Coverage agreed in the SOW |
| Compound supply | Product from the full biocatalysis workflow, where requested | Supplied with Certificate of Analysis | Availability confirmed per project |
Why Biocatalysis, Why Now
Biocatalysis is increasingly used to replace traditional chemistry and to enable more efficient routes to target compounds, with cost-efficiency, sustainability, and regulation acting as market drivers.
Published work continues to expand the range of transformations accessible to enzymes, from selective hydroxylation and methylation to nicotinamide-dependent reductions and oxidations.
Selectivity That Simplifies Routes
Enzymes can act on highly functionalized molecules without protecting-group chemistry, which can shorten synthetic sequences and reduce side-product formation.
- Selective hydroxylation on complex molecules
- Regio- and chemoselective methylation options
- Chiral products in optically active form
Milder Reaction Conditions
Biocatalytic reactions are typically run in mild aqueous conditions with water as the major solvent and often at lower temperatures than conventional chemistry.
- Reduced reliance on hazardous organic solvents
- Lower energy demand from milder conditions
- Biodegradable catalysts
Cost and Supply Considerations
Transition-metal catalysis can be expensive due to limited availability of precious metals and chiral ligands, which is one driver behind developing in-house biocatalytic routes.
- Reduced dependency on external catalyst supply chains
- Cofactor and co-substrate cost addressed by design
- Isolation optimized to protect isolated yield
Getting Started
Share the target transformation, the current route, and the scale you are working toward. We will review feasibility, propose a development path, and define the scope of the first stage.
Early feasibility work can evaluate whether a manufacturing route is viable before significant internal resources are committed.
FAQ
How do you decide between a whole-cell system and an isolated enzyme?
The choice depends on the enzyme class, cofactor dependence, and the intended process format. Cofactor-dependent enzymes are often run as whole-cell systems or with in situ cofactor regeneration, while isolated or immobilized enzymes can suit continuous-flow formats. The format is selected during route definition and confirmed during reaction optimization.
Can you work with an enzyme we already have?
Yes. Programs can start from an existing enzyme or strain, with genome sequencing and analysis, enzyme shortlisting, and library screening used to confirm activity before any property improvement work. If the starting enzyme needs better stability or solvent tolerance, engineering is scoped as part of the same program.
How is cofactor or co-substrate cost handled?
Cofactor dependence and co-substrate cost are treated as central design constraints rather than an afterthought. Regeneration strategies, including whole-cell approaches and in situ regeneration, are evaluated during reaction screening so that the route remains workable as it moves toward larger scale.
What do we receive at the end of a project?
Deliverables are defined in the project SOW and typically include the biocatalyst, an optimized process description covering conditions, substrate loading, and regeneration strategy, an analytical data package, and process documentation to support technology transfer. Where a compound supply is requested, the product can be supplied with a Certificate of Analysis.
Do you support scale-up and technology transfer?
Yes. Scale-up is part of the development path, covering stirred-tank bioreactor operation and, where appropriate, continuous-flow formats. Support is tailored to client needs and can include help with the selection and assessment of scale-up facilities and the generation of process documentation for transfer.
References
- Rodrigues CJC, de Carvalho CCCR. Process Development for Benzyl Alcohol Production by Whole-Cell Biocatalysis in Stirred and Packed Bed Reactors. Microorganisms. 2022;10(5). View on PubMed
- Zell D, Pillon G, Iding H, et al. Stereoselective Synthesis of trans-3-Amino-2,2,4,4-tetramethylcyclobutanol. Organic letters. 2025;27(31):8586-8590. View on PubMed
- Balakrishnan S, Rosenthal K. Cell-free protein synthesis for biocatalysis. Methods in enzymology. 2025;714:445-463. View on PubMed
- Mittmann E, Mickoleit F, Maier DS, et al. A Magnetosome-Based Platform for Flow Biocatalysis. ACS applied materials & interfaces. 2022;14(19):22138-22150. View on PubMed
- Cardoso Marques MP, Lorente-Arevalo A, Bolivar JM. Biocatalysis in Continuous-Flow Microfluidic Reactors. Advances in biochemical engineering/biotechnology. 2022;179:211-246. View on PubMed
- Lundemo MT, Woodley JM. Guidelines for development and implementation of biocatalytic P450 processes. Applied microbiology and biotechnology. 2015;99(6):2465-83. View on PubMed
Discuss Your Biocatalytic Route
Send us the target transformation, your current route, and the scale you are aiming for. We will review feasibility and outline a staged development path covering enzyme, process, and scale-up.