Citation: Zi-Ru Wang, Pei-Yi Liu, Chao Zhang, Zhang-Yuan Yan, Hui-Ming Ge, Ren-Xiang Tan, Zi-Fei Xu. Premature termination in streptovaricin biosynthesis reveals unnatural short-chain analogues[J]. Chinese Chemical Letters, ;2026, 37(6): 112171. doi: 10.1016/j.cclet.2025.112171 shu

Premature termination in streptovaricin biosynthesis reveals unnatural short-chain analogues

Zi-Ru Wang ^{a, 1} ,
Pei-Yi Liu ^{a, 1} ,
Chao Zhang ^a ,
Zhang-Yuan Yan ^a ,
Hui-Ming Ge ^{a, *,} ,
Ren-Xiang Tan ^{a, *,} ,
Zi-Fei Xu ^{a, b, *,}

a.
State Key Laboratory of Pharmaceutical Biotechnology, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Life Sciences, Nanjing University, Nanjing 210023, China
b.
State Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China

hmge@nju.edu.cn

rxtan@nju.edu.cn

xuzifei@mail.kib.ac.cn

Received Date: 19 September 2025
Revised Date: 24 November 2025
Accepted Date: 25 November 2025
Available Online: 25 November 2025

Figures(4)

This study reports the discovery of three shortened streptovaricin analogues, prestreptovaricins A–C (2–4), from Streptomyces spectabilis NA07477. Through comprehensive NMR and HRMS analysis, we elucidated their structures as a linear C13-polyketide (2), a 15-membered (3), and a 17-membered macrolactam (4), representing the first divergence from the character-istic C23 ansa chain in this antibiotic family. Gene inactivation experiments demonstrated that these truncated metabolites result from premature chain release at modules 5–7 of the polyketide synthase, rather than module skipping. Notably, the cyclized products 3 and 4 persisted upon knockout of the dedicated amide synthase stvF, implying catalysis by promiscuous cyclases. Our findings uncover premature termination as a previously unrecognized pathway for structural diversification in ansamycin biosynthesis.
- Ansamycins,
- Streptovaricin,
- Prestreptovaricins A–C,
- Biosynthesis,
- Premature termination
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