Biocatalysis & Enzyme Manufacturing for APIs and Intermediates

Mika Biologics — your scalable, greener route to complex chemistry

Why this service exists

You already rely on microbial platforms and supply enzymes for IVD. Extending that capability to biocatalysis closes a valuable gap for pharma and specialty chemicals. Many chiral centers, late-stage oxidations, and chemo-selective steps are still hard or wasteful using purely chemical routes. Enzymes unlock milder conditions, sharper selectivity, and lower E-factors, but only if the process is engineered end-to-end: discovery, expression, purification, immobilization, reactor choice, cofactor strategy, and quality analytics. Mika Biologics provides a single accountable path from enzyme design to kg–ton biotransformations with a manufacturing system that meets GMP expectations for API intermediates and final steps.

What we deliver (scope recap)

Enzyme discovery and engineering for KREDs, transaminases, nitrilases, BVMOs, and more using directed evolution and AI design
Fermentation to purification including precipitation, TFF, and chromatography, followed by immobilization in packed-bed or CSTR formats
Process development for solvent systems, cofactor recycle, continuous flow, and enzyme recycle with robust space-time yield
Toll manufacturing of enzymes and biotransformations of customer substrates at kg to ton scale
Regulatory and quality coverage including traceability, residuals control, and impurity profiling.

Target transformations

Asymmetric ketone reductions with KREDs to set single or multiple stereocenters
Reductive amination via transaminases including challenging bulky amines or keto acids
Nitrile hydrolysis and amide formation with nitrilases and amidases, avoiding harsh mineral acids
Baeyer–Villiger oxidations with BVMOs to generate lactones and esters with high regioselectivity
Ene-reductase hydrogenations of activated alkenes at low pressure and temperature
Imine reductases for chiral amine construction where metal catalysts struggle
Halohydrin dehalogenases and epoxide hydrolases for ring opening with precise regio- and enantio-control
Glycosylations and late-stage functionalizations using glycosyltransferases, P450s, and peroxygenases
Cascade reactions that chain two or more enzymes to cut isolation steps and improve atom economy.

Catalyst options

We maintain a workhorse panel and develop fit-for-purpose catalysts as needed. Options include KREDs, ATAs (ω-transaminases), nitrilases, amidases, BVMOs, ene-reductases, imine reductases, epoxide hydrolases, halohydrin dehalogenases, monooxygenases such as P450s and UPOs, peroxidases, and laccases. For each class, we can run sequence mining, rational design, and directed evolution. Where timelines demand, we start from our panel and adjust by site-saturation mutagenesis at activity-limiting residues. When screening space is large, we use ML models to prioritize libraries and solvent-compatible motifs.

Reactor and scale strategy

Packed-bed reactors with immobilized enzymes for long campaigns, low leaching, and high space-time yield
CSTRs for free or crosslinked enzymes when fouling risk, solids, or viscosity argues against beds
Continuous flow micro- and meso-reactors for oxygen-limited monooxygenase chemistry and fast heat removal
Two-phase systems or in-situ product removal to manage equilibria or reduce product inhibition
Cofactor regeneration by GDH or FDH for NAD(P)H cycles, IPA coupling for KREDs, and electrochemical or enzymatic H2-driven systems where appropriate
Dissolved oxygen delivery for BVMOs and P450s using high-kLa static mixers, pressurized reactors, or oxygen vectors
Scale brackets from gram development through multi-kilogram batches and continuous campaigns designed for weekly tonnage where feedstock and EHS allow

Process development path

We anchor development in a QTPP → CQA → CPP map so each decision points at clinical or plant needs.

QTPP examples
Target assay and impurity profile for the intermediate or API step
Stereochemical outcome and enantiomeric excess requirements
Residual metals and solvent classes for downstream compliance
Environmental targets such as PMI and E-factor, and cycle time targets for cost of goods

CQAs
Activity and specific productivity of the enzyme under process conditions
Enantioselectivity or diastereoselectivity at release and at end of campaign
Residual enzyme and host protein in the isolated product to meet ICH expectations
Solvent residues, water content, and peroxide or reactive impurity controls for sensitive APIs
Critical intermediate and byproduct limits tied to toxicology

CPPs
pH, temperature, and residence time windows for kinetics and stability
Substrate concentration, addition profile, and mixing regime to avoid local inhibition
Cofactor feed rate or recycle efficiency, GDH/FDH ratio, and glucose or formate load
Oxygen partial pressure or mass transfer coefficients for monooxygenase chemistry
Carrier selection, binding chemistry, and bed velocity for immobilized reactors.

Fermentation, purification, immobilization

Expression hosts include E. coli for rapid iterations, Bacillus for secreted production, and Pichia or other yeasts where glycosylation or secretion benefits activity. We run fed-batch or perfusion as needed, control oxygen transfer and induction timing, and monitor activity inline where feasible.

Purification is matched to the intended use: technical-grade for early route scouting or polished grades for GMP manufacturing support. Options include precipitation, depth filtration, TFF, ion exchange, hydrophobic interaction, and affinity where cost justifies. We design formulations that stabilize the enzyme in solvent-exposed media and during storage, including lyophilized cakes or high-solids liquids.

Immobilization options span covalent binding on epoxy or aldehyde supports, adsorption on hydrophobic carriers, entrapment in gels, CLEAs and crosslinked whole-cell catalysts. We compare pressure drop, mass transfer, leaching, and cleanability to choose the carrier. Reuse cycles are qualified by activity retention, pressure evolution, and leachate testing.

EHS and green metrics

We target greener chemistry by setting quantitative metrics early. PMI and E-factor targets guide solvent choice and recycle strategy. We apply solvent selection guides and substitute Class 1 solvents with Class 2 or 3 where feasible. Waste minimization includes solvent recovery, aqueous phase treatment plans, and salt load reduction. Oxygen service and ATEX compliance are addressed for monooxygenase steps. Enzyme biodegradability and benign degradation are part of the lifecycle assessment. Worker safety, dust control for enzyme powders, and allergen controls are specified in the HAZOP.

Analytics and specifications

Reaction monitoring by HPLC or GC with chiral methods where required
Enantiomeric excess and diastereomer ratios measured by chiral HPLC or GC with orthogonal confirmation
Assay for residual enzyme protein and host DNA in intermediates or APIs as required by specification
Cofactor and byproduct profiles when recycling circuits are used, including residual glucose, formate, or IPA
Residual solvent testing by GC within ICH Q3C limits; water by KF; metals by ICP-MS if chemocatalysis is used in earlier or later steps
Oxidant or peroxide controls for oxygenases and peroxygenases
Thermal and pH stability maps for the enzyme under process solvents
Space-time yield, productivity, and selectivity as process KPIs

Regulatory and quality

We operate under a quality system aligned to ICH Q7 for API steps, with ALCOA+ data integrity across development and manufacturing. Traceability covers enzyme gene lineage, host lot genealogy, fermentation records, purification batches, immobilization carriers, and reactor history. Residuals plans define limits for protein, DNA, catalysts, and solvents in isolated product. Cleaning validation addresses carryover between campaigns, including protein denaturation and swab recovery. Change control captures carrier substitutions, cofactor vendor changes, and solvent swaps with comparability packages. Batch documentation includes master and executed records for biotransformations and for enzyme supply where the enzyme is the deliverable.

Toll manufacturing and capacity

We provide two toll modes. Enzyme toll: we manufacture and ship the catalyst with a certificate covering activity, purity tier, and stabilizer formulation. Biotransformation toll: we receive your substrate, run the step at our site in batch or continuous mode, and ship isolated intermediate or crystallized API with analytical release. Campaign sizes run from multi-kilogram to ton scale depending on substrate hazard class, solvent throughput, and reactor availability. For oxygenase chemistry, continuous packed beds and intensified oxygen delivery units keep throughput up while controlling hazard.

Tech transfer and risk controls

We map your current step, known impurities, and plant constraints. A transfer plan defines minimum data to reproduce activity, mass transfer limits, and deactivation modes. Parallel scale-down models de-risk fouling, emulsion formation, or exotherms. We qualify alternative carriers and solvents to cushion supply risk. For continuous beds, we set criteria for bed replacement, regeneration, and bypass. A deviation playbook covers oxygen outages, cofactor pump failures, and off-spec conversion with containment and rework paths.

Case studies

Bulky ketone to chiral alcohol via KRED
Challenge: low ee using metal catalyst at high pressure.
Solution: KRED screen with ML-prioritized variants; IPA-coupled recycle in CSTR; two-phase system to limit inhibition.
Outcome: 99.5% ee, STY improvement 4×, solvent swap to Class 3 reduced PMI by 35%.

Nitrile to amide with nitrilase
Challenge: mineral-acid hydrolysis generating salt loads and racemization.
Solution: nitrilase route in aqueous buffer; in-line pH control; continuous product extraction.
Outcome: 90% overall yield, eliminated acid waste, simplified work-up.

Baeyer–Villiger oxidation using BVMO
Challenge: mCPBA route with safety and peroxide residue concerns.
Solution: immobilized BVMO packed bed with oxygen mass transfer intensification.
Outcome: controlled oxidation, reduced hazard class, lower peroxide residuals with continuous hold.

FAQs

Can you supply enzymes only or run the whole reaction?
Both. We can ship stabilized enzyme or run toll biotransformations through isolation and release testing.

How do you handle cofactor costs?
We recycle cofactors enzymatically or by simple coupling agents and monitor byproduct accumulation. We design purge steps for spent cofactors.

Do you support continuous manufacturing?
Yes. We run immobilized packed beds and continuous stirred reactors with online analytics and established start-up and shutdown protocols.

What purity tiers can you deliver for enzymes?
Technical grade for development, process-qualified for plant trials, and GMP-aligned documentation for regulated steps. Specifications are set to the use case.

How do you prevent enzyme carryover into the API?
Work-up includes phase separations, washes, and protein precipitation controls. Residual protein and DNA are tested against specification with validated methods.

What if our substrate needs a hazardous solvent?
We design containment, ventilation, and recovery plans, and seek safer alternatives guided by solvent selection frameworks. Where necessary, we isolate the hazard in continuous equipment.

Can you integrate with existing chemocatalysis steps?
Yes. We align solvent, pH, and isolation stages so biocatalysis slots into your current train with minimal revalidation.

How to engage

Discovery call to confirm target step, route constraints, and QTPP
Feasibility plan covering enzyme choice, cofactor strategy, solvent space, and reactor options
Workplan and quote with decision gates, analytics, and projected STY and PMI targets
Kickoff with material readiness, safety review, and pilot schedule.

Summary

Biocatalysis delivers selectivity, milder conditions, and greener metrics—but it only scales when discovery, enzyme supply, immobilization, reactor engineering, and quality live under one roof. As a biocatalysis CDMO, Mika Biologics supplies custom or panel enzymes, builds robust processes with cofactor recycle and continuous options, and manufactures at kg–ton scales with specifications that stand up to regulatory review. Whether you need a single asymmetric reduction or a multi-enzyme cascade, we design for manufacturability from day one and deliver a route that is cleaner, faster, and ready for the plant.

Interested in discussing a project? Email us at info@mikabiologics.com