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- Title
Synthesis of two substrate mimics of thioesterase in the biosynthesis of cyclic depsipeptide WS9326A.
- Authors
Zhongyi Zhang; Hanxuan Wang; Guiyang Wang; Xueyang Ma; Tan Liu; Tongtong Geng; Xiaoxu Sun; Donghui Yang; Suwei Dong; Ming Ma
- Abstract
WS9326A is a tachykinin receptor antagonist and quorum sensing inhibitor discovered from several Streptomyces strains. The structure of WS9326A features a (Z)-pentenylcinnamoyl moiety attached on a cyclic depsipeptide skeleton, which is biosynthesized by nonribosomal peptide synthetases (NRPS). The regioselective cyclization in the last step of NRPS catalysis, which is proposed to be catalyzed by a thioesterase (TE) domain in the last module, has not been experimentally characterized. We here report the synthesis of two substrate mimics (1 and 2) of the TE (WS9326A-TE) in WS9326A biosynthesis, by using Fmoc-based solid-phase peptide synthesis (SPPS) method. Compounds 1 and 2 are new compounds whose structures have been elucidated based on NMR and HRESIMS analyses. The N-terminal cinnamoyl moiety and C-terminal methylated L-Ser moiety in 2 were incorporated under the mild SPPS conditions. Given the isolation difficulties of substrate of WS9326A-TE from the Streptomyces producers of WS9326A, our synthesis of 1 and 2 set the stage for the reconstitution of WS9326A-TE's catalytic reaction in vitro in the future.
- Subjects
NONRIBOSOMAL peptide synthetases; BIOSYNTHESIS; TACHYKININ antagonists; SOLID-phase synthesis; QUORUM sensing
- Publication
Journal of Chinese Pharmaceutical Sciences, 2019, Vol 28, Issue 9, p605
- ISSN
1003-1057
- Publication type
Article
- DOI
10.5246/jcps.2019.09.058