biostudies-literatureUnknown6(2)Jin SPolyester formation by polycondensation in water is limited by an esterification-hydrolysis equilibrium that strongly favors hydrolysis under mild conditions. Although aqueous-phase esterification has been demonstrated with chemical catalysts and isolated enzymes, these systems typically target small-molecule esters or rely on preactivated donors. The polyhydroxyalkanoate (PHA) pathway is the only known native metabolic route for polyester biosynthesis, but it is essentially limited to the polymerization of 3-hydroxybutyrate and related short-chain hydroxyalkanoate monomers. Consequently, realizing efficient aqueous-phase polycondensation to high-molar-mass polyesters remains a major challenge. Here, an intracellular CoA activation/acyltransferase cascade (ACOS5 _<i>At</i> -WS2 <JACS Au1347-1358https://www.ebi.ac.uk/biostudies/studies/S-EPMC12933353biostudies-literatureAqueous-Phase Polycondensation of Hydroxy Fatty Acids via a Whole-Cell CoA Activation-Acyltransferase Cascade.PMC12933353Liu JJin SWu QZhang YBaeyens JLu DWang FNie KDeng LJiang NfalseAqueous-Phase Polycondensation of Hydroxy Fatty Acids via a Whole-Cell CoA Activation-Acyltransferase Cascade.Polyester formation by polycondensation in water is limited by an esterification-hydrolysis equilibrium that strongly favors hydrolysis under mild conditions. Although aqueous-phase esterification has been demonstrated with chemical catalysts and isolated enzymes, these systems typically target small-molecule esters or rely on preactivated donors. The polyhydroxyalkanoate (PHA) pathway is the only known native metabolic route for polyester biosynthesis, but it is essentially limited to the polymerization of 3-hydroxybutyrate and related short-chain hydroxyalkanoate monomers. Consequently, realizing efficient aqueous-phase polycondensation to high-molar-mass polyesters remains a major challenge. Here, an intracellular CoA activation/acyltransferase cascade (ACOS5 _<i>At</i> -WS2 <2026-01-01T00:00:00Z2026 Feb2026-07-16T22:30:40.256Z2026-07-11T03:11:59.479ZS-EPMC129333534175581410.1021/jacsau.5c01683