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The Discovery and Biosynthesis of Nicotinic Myxochelins from an <i>Archangium</i> sp. SDU34

Degao Wang, Luo Niu, Zhao‐Min Lin, Jingjing Wang, Dongfang Gao, Haiyan Sui, Yue‐zhong Li, Changsheng Wu

2021Journal of Natural Products20 citationsDOI

Abstract

Myxobacteria are a prolific source of structurally diverse natural products, and one of the best-studied myxobacterial products is the siderophore myxochelin. Herein, we report two new compounds, myxochelins N (1) and O (2), that are nicotinic paralogs of myxochelin A, from the terrestrial myxobacterium Archangium sp. SDU34; 2 is functionalized with a rare 2-oxazolidinone. A precursor-feeding experiment implied that the biosynthesis of 1 or 2 was due to altered substrate specificity of the loading module of MxcE, which likely accepts nicotinic acid and benzoic acid instead of more conventional 2,3-dihydroxybenzoic acid. We also employed a phylogenomic approach to map the evolutionary relationships of the myxochelin biosynthetic gene clusters (BGCs) in all the available myxobacterial genomes, to pave the way for the future discovery of potentially hidden myxochelin derivatives. Although the biological function of 1 and 2 is unclear yet, this work underpins that even extensively studied BGCs in myxobacteria can still produce new chemistry.

Topics & Concepts

MyxobacteriaBiosynthesisComputational biologyDrug discoveryBiologyFunction (biology)Nicotinic agonistGeneGenomeBiochemistryStereochemistryChemistryGeneticsBacteriaReceptorMicrobial Natural Products and BiosynthesisMarine Sponges and Natural ProductsSlime Mold and Myxomycetes Research
The Discovery and Biosynthesis of Nicotinic Myxochelins from an <i>Archangium</i> sp. SDU34 | Litcius