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.
Gao DW, Jamieson CS, Wang G, Yan Y, Zhou J, Houk KN, Tang Y (2021) A Polyketide Cyclase That Forms Medium-Ring Lactones Journal of the American Chemical Society143: 80-84
Gao DW, Jamieson CS, Wang G, Yan Y, Zhou J, Houk KN, Tang Y (2021) Journal of the American Chemical Society143: 80-84