Discovery of Cytotoxic Barbiturate-Bridged Dimeric Chrolactomycins from <i>Catenulispora acidiphila</i> TX15
Six new spirotetronate polyketides, chrolactomycins A-F (<b>2</b>-<b>7</b>), and the known chrolactomycin (<b>1</b>) were isolated and identified from <i>Catenulispora acidiphila</i> TX15. Chrolactomycins D-F (<b>5</b>-<b>7</b>) feature an unprecedented dimeric skeleton bridged by a rare barbiturate unit. Sequencing and characterization of a type I polyketide synthase biosynthetic gene cluster led to the proposal of a biosynthetic pathway for <b>1</b>-<b>7</b>. Compounds <b>2</b>-<b>4</b> exhibited antibacterial activities, while <b>3</b>-<b>7</b> displayed cytotoxicity to multiple cancer cell lines, with dimer <b>5</b> demonstrating the most potent effects (IC<sub>50</sub> = 2.2-7.7 μM).
Authors
- Xiaoying Bian (ORCID: https://orcid.org/0000-0002-1356-3211)
- Haibo Zhou (ORCID: https://orcid.org/0000-0001-9656-6479)
- Youming Zhang (ORCID: https://orcid.org/0000-0003-3326-9092)
- Yang Liu (ORCID: https://orcid.org/0000-0002-0367-8189)
- Na Zhang (ORCID: https://orcid.org/0000-0002-7578-0465)
- Ping Yan (ORCID: https://orcid.org/0000-0001-7523-9460)
- Xingkun Hao
- Qiyao Shen
Institutions
- Shandong University (CN)
- Czech Academy of Sciences, Institute of Biotechnology (CZ)
- State Key Laboratory of Microbial Technology
Publication Details
- Journal
- Organic Letters
- Published
- 2025-09-03
- DOI
- https://doi.org/10.1021/acs.orglett.5c02941
- Citations
- 2
- Primary Topic
- Microbial Natural Products and Biosynthesis
- Type
- article
- Field-Weighted Citation Impact
- 2.79