Technology · Health & biomedicine / Therapeutics & platforms

Chemoenzymatic API synthesis (biocatalytic small-molecule manufacturing)

Engineered-enzyme steps (transaminases, ketoreductases, lipases) substituted into small-molecule API routes to replace metal-catalysed or multi-step chemical sequences — anchored by Codexis's CodeEvolver platform (the Merck sitagliptin transaminase case) in the US, Almac's biocatalysis CDMO in the UK, Lonza's HPAPI/biocatalysis toolkit in Switzerland, and Asymchem and WuXi AppTec's biocatalysis-enabled CDMO platforms in China.

Maturity 6/9 Risk: low Pharma & biologics US · EU · CN Science: why it works → verified 2026-07-20 · 5 Sources (0 independent)

1 · What it gives

Chemoenzymatic API synthesis replaces one or more steps of a small-molecule active pharmaceutical ingredient (API) route with an engineered enzyme — a transaminase, ketoreductase, lipase or nitrilase — run either as an isolated biocatalyst or a whole-cell biotransformation, then rejoined to conventional chemical steps in a hybrid route. The approach cuts heavy-metal catalyst residues, lowers solvent and step count, and reaches stereochemistry that chemical catalysis struggles with; Codexis’s directed-evolution CodeEvolver platform (transferred to Merck for its own internal manufacturing use) supplied the engineered transaminase that replaced a rhodium-catalysed asymmetric hydrogenation step in sitagliptin (Januvia) manufacture, cutting total waste by roughly 19% and eliminating a heavy-metal catalyst — the field’s reference case. Almac runs immobilised-lipase (CALB) and cGMP flow-hydrogenation biocatalysis for late-stage API process development; Lonza folds biocatalysis into its global small-molecule and HPAPI (highly potent API) CDMO toolkit; and Asymchem and WuXi AppTec (WuXi STA) both offer biocatalysis-enabled green-chemistry platforms inside their broader Chinese CDMO operations serving global pharma sponsors.

The key directions of chemoenzymatic API synthesis are:

Engineered biocatalyst supply (Biocatalysis): directed-evolution or rational-design enzyme variants (transaminases, ketoreductases, imine reductases) sold or licensed as a manufacturing input — Codexis’s CodeEvolver is the reference platform.
Biocatalysis CDMO process development (Biocatalysis CDMO): contract development of a hybrid chemo-enzymatic route for a sponsor’s API, from route scouting through GMP scale-up — Almac, Lonza, Asymchem, WuXi AppTec.
Immobilised and continuous-flow biocatalysis (Immobilized Enzymes): enzymes fixed to solid supports or run in continuous-flow reactors for reuse across cycles and integration with flow chemistry — Almac’s flow-hydrogenation/CALB work.
Route replacement economics (Route Replacement): displacing metal-catalysed asymmetric synthesis or multi-step resolutions with a single enzymatic step, reducing heavy-metal residue, solvent volume and total step count.

Sectoral value chain#

[enzyme discovery/engineering] ──> [route scouting & retrosynthesis] ──> [biocatalyst scale-up]
                                                    │
                                       (GMP chemoenzymatic manufacturing)
                                                    │
                                                    ▼
[API supply & lifecycle mgmt] <─── [purification & DMF/CEP filing] <─────┘

Value chain levels#

Level	Description	Key inputs/outputs
Enzyme Discovery & Engineering	directed evolution / rational design of transaminases, ketoreductases, lipases against a target reaction	In: wild-type enzyme, target substrate. Out: engineered biocatalyst.
Route Scouting & Retrosynthesis	identify which step of a chemical API route an enzyme can replace	In: chemical route, biocatalyst library. Out: hybrid chemoenzymatic route.
Biocatalyst Scale-up	fermentation or immobilisation of the enzyme for manufacturing-scale supply	In: engineered gene, host strain. Out: bulk/immobilised enzyme.
GMP Chemoenzymatic Manufacturing	hybrid batch or continuous-flow process combining enzymatic and chemical steps	In: substrate, biocatalyst. Out: crude API.
Purification & Regulatory Filing	crystallisation, impurity control, EDQM CEP / FDA DMF dossier	In: crude API. Out: GMP API + dossier.
Supply & Lifecycle Management	tech transfer, second-sourcing, patent/FTO management for the enzymatic step	In: validated process. Out: secured commercial supply.

Cross-cutting technologies of the sector:

Directed evolution (Directed Evolution): iterative mutagenesis and high-throughput screening evolves an enzyme’s activity, stability and selectivity toward a non-natural pharmaceutical substrate — the basis of Codexis’s CodeEvolver.
Enzyme engineering (Enzyme Engineering): rational, structure-guided redesign of enzyme active sites to accept API intermediates that the wild-type enzyme cannot process.
Immobilised/continuous-flow biocatalysis (Immobilized Enzymes): fixing enzymes to solid supports enables reuse across reaction cycles and integration into continuous-flow manufacturing trains alongside chemical steps.

2 · What it replaces 0 · matched by industry

No graded substitution linked yet.

3 · How to implement 6 steps

1
Enzyme discovery and engineering
A wild-type enzyme (transaminase, ketoreductase, lipase or nitrilase) is identified against the target reaction, then evolved through directed mutagenesis or redesigned rationally until it accepts the pharmaceutical intermediate at manufacturing-relevant conversion and selectivity.
2
Route scouting and retrosynthesisSynthesis & conversion
Process chemists map the sponsor’s existing (or new) chemical route to the API and identify which step — typically an asymmetric reduction, transamination or resolution — an engineered biocatalyst can replace or improve.
Who can do this step matched automatically
China Everbright Environment Group China
163,050 tonnes
“Uniquely equipped with the credentials for the R&D, design, and production of both high-efficiency dust filtration materials and SCR denitration catalysts, as well as for the …”
SyncoZymes (Shanghai) China
1,200 tons industrial scale
“is a biotechnology company specializing in green pharmaceutical technology, biocatalysis, and synthetic biology.”
Godavari Biorefineries (NSE) India
industrial scale
“Godavari Biorefineries Limited is an Indian integrated biorefinery producing ethanol, bio-based chemicals, sugar, and power.”
3
Biocatalyst scale-upSynthesis & conversionContract manufacturing (CMO/CDMO)
The engineered enzyme gene is expressed in a production host and fermented at scale, or the purified enzyme is immobilised on a solid support, to supply the manufacturing-scale biocatalyst.
Who can do this step matched automatically
Ajinomoto Japan
✓ GMP industrial scale
“It remains highly active, focusing on its 2030 roadmap through business model transformation and expansion in CDMO services and high-value-added materials.”
Nissan Chemical Japan
industrial scale
“Healthcare and contract manufacturing: Pharmaceuticals and medical materials, including healthcare products and custom chemicals (contract manufacturing of pharmaceutical …”
China Everbright Environment Group China
163,050 tonnes
“Uniquely equipped with the credentials for the R&D, design, and production of both high-efficiency dust filtration materials and SCR denitration catalysts, as well as for the …”
SyncoZymes (Shanghai) China
1,200 tons industrial scale
“is a biotechnology company specializing in green pharmaceutical technology, biocatalysis, and synthetic biology.”
Space F South Korea
“Space Rintec's Blueprint for Space CRO and CDMO - EDAILY — Space Rintech (Space Lintech) plans full-scale commercialization of its space CRO/CDMO business next year, targeting 10 …”
4
GMP chemoenzymatic manufacturingContract manufacturing (CMO/CDMO)
The enzymatic step is run in batch or continuous-flow mode and rejoined to the remaining conventional chemical steps under cGMP, producing the crude API with the metal-catalyst or multi-step-resolution burden of the original route removed.
Who can do this step matched automatically
Ajinomoto Japan
✓ GMP industrial scale
“It remains highly active, focusing on its 2030 roadmap through business model transformation and expansion in CDMO services and high-value-added materials.”
Nissan Chemical Japan
industrial scale
“Healthcare and contract manufacturing: Pharmaceuticals and medical materials, including healthcare products and custom chemicals (contract manufacturing of pharmaceutical …”
SyncoZymes (Shanghai) China
1,200 tons industrial scale
“CRO/CDMO Services”
Space F South Korea
“Space Rintec's Blueprint for Space CRO and CDMO - EDAILY — Space Rintech (Space Lintech) plans full-scale commercialization of its space CRO/CDMO business next year, targeting 10 …”
Esco Aster Singapore
5,000 L industrial scale
“Esco Aster (Singapore) is a cGMP contract research, development and manufacturing organization (CRDMO/CDMO) and bioinnovation venture accelerator that helps clients and …”
5
Purification and regulatory filingPurification & downstream
The API is crystallised and impurity-profiled, with the enzymatic step documented in the CMC package supporting an EDQM Certificate of Suitability (CEP) or FDA Drug Master File (DMF) under ICH Q11 development guidance.
Who can do this step matched automatically
Advanced Enzyme Technologies (NSE) India
✓ GMP 500 m3
“Development of robust, scalable fermentation and downstream processing (production and recovery/yield optimization).”
HLB Genex (ex-GenoFocus) South Korea
industrial scale
“With fungal and bacterial secretion systems, we custom produce the evolved enzyme products in large-scale fermentation and downstream processes.”
SyncoZymes (Shanghai) China
1,200 tons industrial scale
“CRO/CDMO and Testing/Quality Research Services: Comprehensive contract research and development, analytical, and quality assessment capabilities with access to NMR, LC-MS, GC-MS, …”
Space F South Korea
“2026-07-12 [Korea's next drug lab is in orbit - The Korea Herald — Space LiinTech is advancing Korea’s foray into space-based drug research with autonomous microgravity platforms …”
Esco Aster Singapore
5,000 L industrial scale
“Adherent cell culture and downstream processing: commercialized Tide Motion bioreactor platform (MiniTide to TideXcell) with closed automated cell harvesting and single-use …”
Algal Bio Japan
industrial scale
“・Equipped with comprehensive downstream processing capabilities (Concentration, sterilization, and drying)”
6
Supply and lifecycle management
Sponsors manage tech transfer, second-sourcing and freedom-to-operate for the enzymatic step across the commercial life of the API, with the CDMO or enzyme supplier (Codexis, Almac, Lonza, Asymchem, WuXi STA) typically retaining the biocatalyst IP.

4 · Who delivers

Matched suppliers (matched automatically)

SyncoZymes (Shanghai)	China	Producer	active
Codexis	United States	Producer	active
HLB Genex (ex-GenoFocus)	South Korea	Producer	active
Evogene (NASDAQ: EVGN)	Israel	Not classified	active
Solugen	United States	Producer	active
Tsingke Biotechnology	China	Producer	active
Nature Energy	Denmark	Producer	active

Leading companies and institutes (from the brief)

Company / Institute	Country	Key products / platforms	Tech features	Status 2026
Codexis	🇺🇸 USA	CodeEvolver engineered enzymes	Directed-evolution transaminase (sitagliptin case)	commercial
Almac	🇬🇧 UK	Biocatalysis CDMO	Immobilised CALB, flow hydrogenation	commercial
Lonza	🇨🇭 Switzerland	Small-molecule / HPAPI CDMO	Biocatalysis within broader process toolkit	commercial
Asymchem	🇨🇳 China	Biocatalysis-enabled CDMO	Green-chemistry enzymatic routes	commercial
WuXi AppTec	🇨🇳 China	WuXi STA biotransformation platform	Biocatalysis within CMC service line	commercial

5 · Rules & route to market

United States

The US anchors the reference chemoenzymatic-API platform business, led by Codexis’s engineered-enzyme licensing and supply model.

CodeEvolver, sitagliptin transaminase, FDA DMF#

Codexis CodeEvolver platform: a directed-evolution enzyme-engineering platform that has produced transaminases, ketoreductases and other biocatalysts for API manufacturing; Codexis completed the transfer of CodeEvolver technology to Merck for Merck’s own internal process-development use.
Sitagliptin transaminase case: Codexis and Merck’s engineered transaminase route to sitagliptin (Januvia) replaced a rhodium-catalysed asymmetric hydrogenation, the reference case for chemoenzymatic API manufacturing cited across the industry; Codexis and Merck have since amended and extended their supply agreement for the enzyme.
FDA DMF framework: chemoenzymatic API routes enter US supply chains under FDA Drug Master Files, with the enzymatic step documented alongside conventional chemical unit operations in the CMC package.

European Union

Europe’s chemoenzymatic-API tier spans a UK biocatalysis specialist CDMO (Almac) and a Swiss global CDMO folding biocatalysis into a broader small-molecule and HPAPI toolkit (Lonza).

Almac, Lonza, EDQM#

Almac (Craigavon, UK): an API chemical-development CDMO running immobilised-lipase (CALB) biocatalysis and cGMP flow-hydrogenation capability for late-stage sponsor process development.
Lonza (Visp, Switzerland): a global small-molecule and highly-potent-API (HPAPI) CDMO that includes biocatalysis among its process-development toolkit, expanding its Visp manufacturing capacity.
EDQM CEP framework: chemoenzymatic API routes enter the EU supply chain under European Directorate for the Quality of Medicines (EDQM) Certificates of Suitability (CEP) and ICH Q11 development-and-manufacture guidance.

China

China hosts large-scale CDMO capacity offering biocatalysis-enabled green-chemistry routes alongside conventional chemical synthesis, led by Asymchem and WuXi AppTec (WuXi STA).

Asymchem, WuXi STA, NMPA#

Asymchem (凯莱英): a major Chinese CDMO whose biocatalysis-enabled green-chemistry platform sits alongside conventional chemical synthesis for global pharma API and intermediate manufacturing.
WuXi AppTec / WuXi STA (药明康德): the small-molecule CDMO division WuXi STA offers a biotransformation/biocatalysis platform within its broader chemistry, manufacturing and controls (CMC) service line for global sponsors.
Domestic cluster: China’s large-molecule and small-molecule CDMO base has progressively added enzymatic and biocatalytic route options to compete on cost and green-chemistry credentials for export-oriented API manufacturing.
NMPA framework: chemoenzymatic API manufacturing for export runs under NMPA cGMP inspection, with dossiers filed in parallel for FDA/EDQM and other destination-market regulators.

6 · Money: tenders & grants

Grant	Crafting routes to a circular economy European Commission · EU	Sep 23, 2027 342 days
Grant	Development of cell-free protein synthesis platforms for discovery and/or production of biologicals European Commission · EU	Apr 13, 2027 179 days
Grant	Open topic: Using the Circular Cities and Regions Initiative to strengthen urban manufacturing in support of … European Commission · EU	Apr 8, 2027 174 days
Grant	Textile circularity through advanced processing and manufacturing technologies and system approaches (IA) … European Commission · EU	Feb 2, 2027 109 days

7 · Tech stack & innovations

The stack pairs directed-evolution and rational enzyme engineering with immobilisation/continuous-flow process engineering to insert a single high-selectivity biocatalytic step into an otherwise conventional chemical API route.

Directed evolution and enzyme engineering (Directed Evolution):
- Iterative mutagenesis and high-throughput screening (Codexis’s CodeEvolver) evolves transaminases, ketoreductases and other enzymes to accept non-natural pharmaceutical intermediates, replacing metal-catalysed asymmetric steps.
Biocatalysis CDMO process development (Biocatalysis CDMO):
- Almac, Lonza, Asymchem and WuXi STA scout a sponsor’s chemical route for a step an enzyme can replace, then scale the hybrid chemoenzymatic process to GMP.
Immobilised and continuous-flow biocatalysis (Immobilized Enzymes):
- Almac’s immobilised-CALB and flow-hydrogenation work fixes the enzyme to a solid support or reactor, enabling reuse across cycles and direct integration with downstream chemical flow steps.
Route-replacement economics (Route Replacement):
- A single enzymatic step can displace a multi-step chemical resolution or a heavy-metal-catalysed hydrogenation, cutting solvent volume, step count and catalyst-residue burden — the basis of the sitagliptin case’s reported waste reduction.

Sources 5 · 0 independent · 5 producer sites

Producers' own sites 5

Codexis producer checked 2026-07-09 · link not kept
Almac producer checked 2026-06-11 · link not kept
Lonza producer checked 2026-07-06 · link not kept
Asymchem producer checked 2026-07-20 · link not kept
Wuxi apptec producer checked 2026-07-20 · link not kept