Open AccessA Polyketide Cyclase That Forms Medium-Ring Lactones
Author(s) -
DeWei Gao,
Cooper S. Jamieson,
Gaoqian Wang,
Yan Yan,
Jiahai Zhou,
K. N. Houk,
Yi Tang
Publication year - 2020
Publication title -
journal of the american chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.115
H-Index - 612
eISSN - 1520-5126
pISSN - 0002-7863
DOI - 10.1021/jacs.0c11226
Subject(s) - chemistry , polyketide , ring (chemistry) , stereochemistry , biocatalysis , substrate (aquarium) , catalysis , enzyme , thioesterase , cyclase , combinatorial chemistry , biosynthesis , organic chemistry , reaction mechanism , oceanography , geology
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.