Lian Duan, Shoufeng Wang, Rijing Liao, Wen Liu
文献索引：Chem. Biol. 19(4) , 443-8, (2012)
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Thiostrepton (TSR), often referred as to a parent compound in the thiopeptide family, is a bimacrocyclic member that features a quinaldic acid (QA) moiety-containing side ring appended to the characteristic core system. QA biosynthesis requires an unusual ring-expanding conversion, showing a methyl transfer onto and a rearrangement of the indole part of L-tryptophan to give a quinoline ketone. Herein, we report that the process involves the activities of the radical methyltransferase TsrT, aminotransferase TsrA, dehydrogenase TsrE, and cyclase TsrD. TsrU, a stereospecific oxidoreductase, catalyzes the further conversion of the ketone into an enantiomerically pure S-alcohol. Elucidation of this chemistry, which is common in the biosynthesis of a number of thiopeptides sharing a QA side ring system, facilitates analog generation, as shown by the achievement of region-specific fluorination of thiostrepton with the improved antibacterial activity.Copyright © 2012 Elsevier Ltd. All rights reserved.
