Structural identification of pyridinopyrone compounds with anti-neuroinflammatory activity from streptomyces sulphureus DSM 40104

Front Microbiol. 2023 Jun 1:14:1205118. doi: 10.3389/fmicb.2023.1205118. eCollection 2023.

Abstract

This study investigated the chemical composition and biosynthesis pathway of compounds produced by Streptomyces sulphureus DSM 40104. With the guild of molecular networking analysis, we isolated and identified six uncommon structural characteristics of compounds, including four newly discovered pyridinopyrones. Based on genomic analysis, we proposed a possible hybrid NRPS-PKS biosynthesis pathway for pyridinopyrones. Notably, this pathway starts with the use of nicotinic acid as the starting unit, which is a unique feature. Compounds 1-3 exhibited moderate anti-neuroinflammatory activity against LPS-induced BV-2 cell inflammation. Our study demonstrates the diversity of polyene pyrone compounds regarding their chemical structure and bioactivity while providing new insights into their biosynthesis pathway. These findings may lead to the development of new treatments for inflammation-related diseases.

Keywords: anti-neuroinflammatory; biosynthesis; polyene pyrone; polyketide; streptomyces.

Grants and funding

This study was financially supported by the National Key R&D Program of China (2018YFA0903200), the Natural Science Foundation of Shaanxi Province (2022JQ-142), the PI Project of Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou) (2021HJ01 and HJRC2022001), and the Hong Kong Branch of Southern Marine Science and Engineering Guangdong Laboratory (Guangdong) (MSEGL20SC01).