Enhancing ω-transaminase catalysis of bulky substrates guided by binding mechanism.

Nature Communications · 14 Oct 2026 · Journal Article · Open access

Teng, Yu + more

The abstract is read at the publisher; the summary is JClub's.

The engineered ω-transaminase variant 13M from Bacillus megaterium achieves 106× higher catalytic activity than wild type while producing ABP with >99% enantiomeric excess.

Why it matters: Bulky ketone precursors like ABP’s precursor are hard for ω-transaminases to bind productively, limiting enzymatic asymmetric synthesis of key pharmaceutical intermediates.
What they did: The team combined Funnel metadynamics, PathDetect-SOM, and path collective variables to map substrate-binding free-energy landscapes, then used dynamic cross-correlation networks to locate distal regulatory sites and iteratively optimized the enzyme.
The result: The 13M variant enables efficient enzymatic asymmetric synthesis of ABP, and the computational–experimental workflow is positioned as a general approach to engineer ω-transaminases for bulky substrates.

AI summary of the abstract · may contain errors · not medical advice · read the paper.

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Enhancing ω-transaminase catalysis of bulky substrates guided by binding mechanism.

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