title: Identification of two novel anti-fibrotic benzopyran compounds produced by engineered strains derived from Streptomyces xiamenensis M1-94P that originated from deep-sea sediments.
abstract: The benzopyran compound obtained by cultivating a mangrove-derived strain, Streptomyces xiamenensis strain 318, shows multiple biological effects, including anti-fibrotic and anti-hypertrophic scar properties. To increase the diversity in the structures of the available benzopyrans, by means of biosynthesis, the strain was screened for spontaneous rifampicin resistance (Rif), and a mutated rpsL gene to confer streptomycin resistance (Str), was introduced into the S. xiamenensis strain M1-94P that originated from deep-sea sediments. Two new benzopyran derivatives, named xiamenmycin C (1) and D (2), were isolated from the crude extracts of a selected Str-Rif double mutant (M6) of M1-94P. The structures of 1 and 2 were identified by analyzing extensive spectroscopic data. Compounds 1 and 2 both inhibit the proliferation of human lung fibroblasts (WI26), and 1 exhibits better anti-fibrotic activity than xiamenmycin. Our study presents the novel bioactive compounds isolated from S. xiamenensis mutant strain M6 constructed by ribosome engineering, which could be a useful approach in the discovery of new anti-fibrotic compounds.
authors.affiliation: State Key Laboratory of Microbial Metabolism and School of Life Science & Biotechnology, State Key Laboratory of Ocean Engineering, Shanghai Jiao Tong University, Shanghai 200240, China. xujunn@sjtu.edu.cn.
authors.forename: Zhong-Yuan
authors.initials: ZY
authors.lastname: You
authors.forename: Ya-Hui
authors.initials: YH
authors.lastname: Wang
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Zhang
authors.forename: Min-Juan
authors.initials: MJ
authors.lastname: Xu
authors.forename: Shu-Jie
authors.initials: SJ
authors.lastname: Xie
authors.forename: Tie-Sheng
authors.initials: TS
authors.lastname: Han
authors.forename: Lei
authors.initials: L
authors.lastname: Feng
authors.forename: Xue-Gong
authors.initials: XG
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
mesh_terms: D001578:Benzopyrans / Q000737:chemistry* / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects; D005355:Fibrosis / Q000188:drug therapy; D019015:Geologic Sediments / Q000737:chemistry* / Q000382:microbiology*; D006801:Humans; D008168:Lung / Q000187:drug effects; D009154:Mutation / Q000235:genetics; D012270:Ribosomes / Q000235:genetics; D013302:Streptomyces / Q000737:chemistry* / Q000235:genetics*; D013912:Threonine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology
chemical_list: D001578:Benzopyrans; C582113:N-((3,4-dihydro-3-hydroxy-2-methyl-2-(4'-methyl-3'-pentenyl)-2H-1-benzopyran-6-yl)carbonyl)threonine; D013912:Threonine