title: A linear hydroxymethyl tetramate undergoes an acetylation-elimination process for exocyclic methylene formation in the biosynthetic pathway of pyrroindomycins.
abstract: We herein report the isolation and characterization of a key linear intermediate in the biosynthetic pathway of pyrroindomycins, the potent spirotetramate natural products produced by Streptomyces rugosporus. This polyene intermediate bears a γ-hydroxymethyl group that is exocyclic to the tetramate moiety, indicating that a serine residue serves as the three-carbon unit for tetramate formation and chain-elongation termination. The further conversion involves an acetylation-elimination of the exocyclic γ-hydroxymethyl group to generate a γ-methylene group, which is indispensable for intramolecular [4 + 2] cross-bridging to construct the characteristic pentacyclic core. The findings presented in this study provide new insights into the biosynthesis of pyrroindomycins, and thus suggest a common paradigm for both spirotetramates and spirotetronates in processing the exocyclic γ-hydroxymethyl group of the five-membered heterocycle.
authors.affiliation: State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China. tiantou81@hotmail.com wliu@mail.sioc.ac.cn.
authors.forename: Qingfei
authors.identifier: http://orcid.org/0000-0002-8397-3507
authors.initials: Q
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China. tiantou81@hotmail.com wliu@mail.sioc.ac.cn.
authors.forename: Zhuhua
authors.initials: Z
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China. tiantou81@hotmail.com wliu@mail.sioc.ac.cn and Research Center for Marine Drugs, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China. tiantou81@hotmail.com wliu@mail.sioc.ac.cn and Huzhou Center of Bio-Synthetic Innovation, 1366 Hongfeng Road, Huzhou 313000, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China. tiantou81@hotmail.com wliu@mail.sioc.ac.cn.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Tian
authors.affiliation: State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China. tiantou81@hotmail.com wliu@mail.sioc.ac.cn and Huzhou Center of Bio-Synthetic Innovation, 1366 Hongfeng Road, Huzhou 313000, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
mesh_terms: D000107:Acetylation; D001688:Biological Products / Q000378:metabolism; D053898:Biosynthetic Pathways; D018942:Macrolides / Q000378:metabolism*; D008697:Methane / Q000031:analogs & derivatives / Q000378:metabolism; D008745:Methylation; D013302:Streptomyces / Q000378:metabolism*
chemical_list: D001688:Biological Products; D018942:Macrolides; C091121:pyrroindomycin A; C030011:carbene; D008697:Methane