The first β-lactone synthetase enzyme is reported, creating an unexpected link between the biosynthesis of olefinic hydrocarbons and highly functionalized natural products. The enzyme OleC, involved in the microbial biosynthesis of long-chain olefinic hydrocarbons, reacts with syn- and anti-β-hydroxy acid substrates to yield cis- and trans-β-lactones, respectively. Protein sequence comparisons reveal that enzymes homologous to OleC are encoded in natural product gene clusters that generate β-lactone rings, suggesting a common mechanism of biosynthesis.
Bibliographical noteFunding Information:
This work was supported by a University of Minnesota Biotechnology Institute Microbial Factories Award (L.P.W. and C.M.W.), the National Institutes of Health (NIH) Training for Future Biotechnology Development (2T32GM008347-22) (J.K.C.), NIH Chemistry-Biology Interface Training Grant GM-008700 (M.R.J.), and an NSF-LSSURP grant (J.Y.N.). Notes The authors declare no competing financial interest.