2. Academic Validation
  3. Discovery and Biosynthetic Studies of a Highly Reduced Cinnamoyl Lipid, Tripmycin A, from an Endophytic Streptomyces sp

Discovery and Biosynthetic Studies of a Highly Reduced Cinnamoyl Lipid, Tripmycin A, from an Endophytic Streptomyces sp

  • J Nat Prod. 2023 Jul 28;86(7):1870-1877. doi: 10.1021/acs.jnatprod.3c00199.
Jieqian Kong 1,  Chengshuang Huang 1,  Yi Xiong 1,  Baihuan Li 1,  Wenping Kong 1,  Wangyang Liu 2,  Zhouke Tan 2,  Dian Peng 2,  Yanwen Duan 1 3,  Xiangcheng Zhu 1 3
Affiliations

Affiliations

  • 1 Xiangya International Academy of Translational Medicine, Central South University, Changsha, Hunan 410013, People's Republic of China.
  • 2 School of Pharmacy, Changsha Health Vocational College, Changsha, Hunan 410605, People's Republic of China.
  • 3 Hunan Engineering Research Center of Combinatorial Biosynthesis and Natural Product Drug Discovery, National Engineering Research Center of Combinatorial Biosynthesis for Drug Discovery, Changsha, Hunan 410011, People's Republic of China.
PMID: 37462318 DOI: 10.1021/acs.jnatprod.3c00199
Abstract

A Tripterygium wilfordii endophyte, Streptomyces sp. CB04723, was shown to produce an unusually highly reduced cytotoxic cinnamoyl lipid, tripmycin A (1). Structure-activity relationship studies revealed that both the cinnamyl moiety and the saturated fatty acid side chain are indispensable to the over 400-fold cytotoxicity improvement of 1 against the triple-negative breast Cancer cell line MDA-MB-231 compared to 5-(2-methylphenyl)-4-pentenoic acid (2). Bioinformatical analysis, gene inactivation, and overexpression revealed that Hxs15 most likely acted as an enoyl reductase and was involved with the side chain reduction of 1, which provides a new insight into the biosynthesis of cinnamoyl lipids.

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