Biocatalysis in petrochemistry

Biocatalysis in petrochemistry deploys engineered enzymes, whole-cell catalysts and cell-free systems to take over synthesis steps that classical petrochemistry still runs over metal and acid catalysts at high temperature and pressure. The enzymatic routes run under mild, near-ambient conditions yet deliver enantioselectivities above 99% ee for chiral building blocks, and immobilized lipases such as CalB hold yields above 95% across many reuse cycles without heavy metals. The addressable industrial-enzyme market spans roughly €20 billion in applications, with the leading biosolutions supplier holding about 48% of the industrial-enzyme share. Where cell-free synthesis is used, protein yields reach up to 3.7 g/L at roughly $39 per gram — a 95% cut in reagent cost — letting biology step directly into continuous petrochemical operation rather than staying at the test-tube scale.

The key directions of biocatalysis in petrochemistry are:

1. Engineered biocatalysts for platform & fine chemicals (Engineered Biocatalysts): machine-learning-driven enzyme engineering (CodeEvolver, roughly one-week design-build-test cycles, an 850+ patent estate) produces chiral amines, alcohols and APIs that replace multi-step thermochemical routes; the portfolio already backs 13 licensed branded pharmaceutical products.
2. Chemoenzymatic cascades for petrochemical building blocks (Chemoenzymatic Cascades): one-pot combinations of chemocatalysis and enzymes valorize biomass and fossil-derived intermediates into aromatics (trans-cinnamic and p-coumaric acid via engineered PAL/TAL) and into high-energy-density polycyclopropanated fatty acids (POP-FAs) for aviation biofuels.
3. Immobilized & cell-free biocatalysis at scale (Immobilized & Cell-Free): reusable immobilized CalB reactors operate at multi-tonne scale for active pharmaceutical ingredients, while cell-free systems reach 3.7 g/L at about $39/g, moving enzymatic catalysis into continuous flow.
4. De novo enzyme design for new-to-nature reactions (De Novo Design): catalytic-motif scaffolding plus diffusion models (TRL 4) create enzymes for reactions no natural enzyme performs — 99% ee and stable above 90°C — unlocking petrochemical targets outside biology’s existing repertoire.

Sectoral value chain#

[Biocatalyst R&D] ──> [Fermentation] ──> [Immobilization] ──> [Biocatalytic conversion]
                              │
                    (submerged or cell-free)
                              │
                              ▼
[Drop-in chemical] <─── [Cascade + recovery] <─────┘

Value chain levels#

Cross-cutting technologies of the sector:

• ML enzyme engineering (CodeEvolver / Directed Evolution): machine-learning plus bioinformatics plus automated lab compress design-build-test to about one week, trained on 20+ years of experimental data.
• Immobilized & cell-free biocatalysis (Immobilized CalB / Cell-Free): reusable immobilized lipases and cell-free lysates move enzymatic catalysis into continuous, heavy-metal-free operation.
• De novo computational enzyme design (De Novo Design): catalytic-motif scaffolding with diffusion and atomistic refinement produces active enzymes for reactions outside nature’s repertoire.

The petrochemical biocatalysis stack is built on protein engineering, computational design and continuous-flow biocatalysis, with machine learning now compressing the path from a new reaction to a manufacturable catalyst.

1. ML-driven enzyme engineering (CodeEvolver / Directed Evolution):
   • Machine learning plus bioinformatics plus automated lab deliver roughly one-week design-build-test cycles, trained on 20+ years of proprietary data rather than public datasets alone.
   • An 850+ patent estate (with 2026 transaminase patents for chiral compounds) underpins a portfolio supporting 13 licensed branded pharmaceutical products and the ECO Synthesis enzymatic RNA/siRNA platform.
2. Immobilized & cell-free biocatalysis (Immobilized CalB / Cell-Free):
   • Immobilized CalB (Candida antarctica lipase B), partnered with Almac, runs esterification and transesterification at multi-kilogram to tonne scale, reusable across cycles under mild, heavy-metal-free conditions at yields above 95%.
   • Cell-free protein synthesis reaches up to 3.7 g/L at about $39/g — a 95% reagent-cost reduction — and machine-learning-guided spatial enzyme assembly lifts cell-free flavonoid titers to 439.42 mg/L.
3. De novo computational enzyme design (De Novo Design):
   • Catalytic-motif scaffolding with a hybrid diffusion/atomistic pipeline (Riff-Diff, LigandMPNN, FastRelax, ESM/AlphaFold), at TRL 4 with acib and Graz University of Technology, yields active, enantioselective enzymes (99% ee) stable above 90°C from only a few dozen sequences.
   • ProteinMPNN-based sequence redesign of glycosyltransferases lifted fed-batch titers to 2.11 g/L cichoriin and 4.05 g/L aesculin, a generalizable route for difficult-to-express enzymes in microbial cell factories.