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Pattern-Based Genome Mining Guides Discovery of the Antibiotic Indanopyrrole A from a Marine Streptomycete

delete2024-11-22
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OA
AI
D
Douglas Sweeney
A
Alexander Bogdanov
A
Alexander B. Chase
G
Gabriel Castro‐Falcón
A
Alma Trinidad-Javier
S
Samira Dahesh
V
Victor Nizet
P
Paul R. Jensen *
DOI:10.1021/acs.jnatprod.4c00934delete
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Abstract

Abstract

En 中文
Terrestrial actinomycetes in the genus Streptomyces have long been recognized as prolific producers of small-molecule natural products, including many clinically important antibiotics and cytotoxic agents. Although Streptomyces can also be isolated from marine environments, their potential for natural product biosynthesis remains underexplored. The MAR4 clade of largely marine-derived Streptomyces has been a rich source of novel halogenated natural products of diverse structural classes. To further explore the biosynthetic potential of this group, we applied pattern-based genome mining, leading to the discovery of the first halogenated pyrroloketoindane natural products, indanopyrrole A (1) and B (2), and the bioinformatic linkage of these compounds to an orphan biosynthetic gene cluster (BCG) in 20 MAR4 genomes. Indanopyrrole A displays potent broad-spectrum antibiotic activity against clinically relevant pathogens. A comparison of the putative indanopyrrole BGC with that of the related compound indanomycin provides new insights into the terminal cyclization and offloading mechanisms in pyrroloketoindane biosynthesis. Broader searches of public databases reveal the rarity of this BGC while also highlighting opportunities for discovering additional compounds in this uncommon class.
Keywords:
NONRIBOSOMAL PEPTIDE
GENE CLUSTERS
EFFLUX PUMPS
X-14547A
DATABASE
BIOSYNTHESIS
FERMENTATION
STAWAMYCIN
RESISTANCE
TAXONOMY
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Journal

Journal of Natural Products cover
Journal of Natural Products
IF:
3.6
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1.2W
Citations:
2.9W

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S
Scripps Institution of Oceanography
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University of California System cover
University of California System
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University of California San Diego
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