Chembiochem. 2026 Jul 29;27(14):e70474. doi: 10.1002/cbic.70474.

ABSTRACT

Efficient, selective, and sustainable synthetic platforms are increasingly important in modern chemical manufacturing, yet chemical flexibility often remains limited. In this study, we develop a modular biocatalytic system for the divergent and continuous transformation of ethyl acetoacetate (EAA) into either enantiomerically pure (R)-3-hydroxybutyric acid ((R)-3HBA) or oligomers of (R)-poly(3-hydroxybutyrate) (PHB). The cascade combines two telescoped packed-bed reactors containing an immobilized, self-sufficient Lactobacillus kefir ketoreductase (LkKRED) and commercial immobilized Candida antarctica lipase B (N435). By simply tuning the reaction conditions, the system selectively directs the substrate toward either product. Under aqueous conditions, it achieves quantitative conversion to (R)-3HBA with >99% enantiomeric excess and maintains excellent stability over 7 days of continuous operation. It also reaches a maximum space-time yield of 105 g L^-1 h^-1, which is 33 times higher than the volumetric productivity of the sequential two-pot process. Under anhydrous conditions, the same setup promotes polycondensation into PHB oligomers, as confirmed by matrix-assisted laser desorption/ionization time-of-flight analysis. Overall, this platform combines productivity, stereoselectivity, and flexibility for the integrated synthesis of chiral building blocks or oligomers.

PMID:42496064 | DOI:10.1002/cbic.70474