A Polyketide Cyclase That Forms Medium-Ring Lactones
De‐Wei Gao, Cooper S. Jamieson, Gao‐Qian Wang, Yan Yan, Jiahai Zhou, K. N. Houk, Yi Tang
Abstract
Medium-ring lactones are synthetically challenging due to unfavorable energetics involved in cyclization. We have discovered a thioesterase enzyme DcsB, from the decarestrictine C1 (1) biosynthetic pathway, that efficiently performs medium-ring lactonizations. DcsB shows broad substrate promiscuity toward linear substrates that vary in lengths and substituents, and is a potential biocatalyst for lactonization. X-ray crystal structure and computational analyses provide insights into the molecular basis of catalysis.
Topics & Concepts
ChemistryPolyketideRing (chemistry)StereochemistryBiocatalysisSubstrate (aquarium)CatalysisEnzymeThioesteraseCyclaseCombinatorial chemistryBiosynthesisOrganic chemistryReaction mechanismGeologyOceanographyMicrobial Natural Products and BiosynthesisFungal Biology and ApplicationsChemical synthesis and alkaloids