Dataset Information

Discovery and Biosynthesis of Clostyrylpyrones from the Obligate Anaerobe Clostridium roseum.

ABSTRACT: Anaerobic bacteria are a promising new source for natural product discovery. Examination of extracts from the obligate anaerobe Clostridium roseum led to the discovery of a new family of natural products, the clostyrylpyrones. The polyketide synthase-based biosynthetic mechanism of clostyrylpyrones is further proposed on the basis of bioinformatic, gene knockout, biochemical analysis, and heterologous expression studies.

SUBMITTER: Li JS

PROVIDER: S-EPMC7655672 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Discovery and Biosynthesis of Clostyrylpyrones from the Obligate Anaerobe <i>Clostridium roseum</i>.

Li Jeffrey S JS Du Yongle Y Gu Di D Cai Wenlong W Green Allison A Ng Samuel S Leung Alexander A Del Rio Flores Antonio A Zhang Wenjun W

Organic letters 20201014 21

Anaerobic bacteria are a promising new source for natural product discovery. Examination of extracts from the obligate anaerobe <i>Clostridium roseum</i> led to the discovery of a new family of natural products, the clostyrylpyrones. The polyketide synthase-based biosynthetic mechanism of clostyrylpyrones is further proposed on the basis of bioinformatic, gene knockout, biochemical analysis, and heterologous expression studies. ...[more]

PMID: 33052676

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Project description:The peroxide response-inducible genes ahpCF, dps, and katB in the obligate anaerobe Bacteroides fragilis are controlled by the redox-sensitive transcriptional activator OxyR. This is the first functional oxidative stress regulator identified and characterized in anaerobic bacteria. oxyR and dps were found to be divergently transcribed, with an overlap in their respective promoter regulatory regions. B. fragilis OxyR and Dps proteins showed high identity to homologues from a closely related anaerobe, Porphyromonas gingivalis. Northern blot analysis revealed that oxyR was expressed as a monocistronic 1-kb mRNA and that dps mRNA was approximately 500 bases in length. dps mRNA was induced over 500-fold by oxidative stress in the parent strain and was constitutively induced in the peroxide-resistant mutant IB263. The constitutive peroxide response in strain IB263 was shown to have resulted from a missense mutation at codon 202 (GAT to GGT) of the oxyR gene [oxyR(Con)] with a predicted D202G substitution in the OxyR protein. Transcriptional fusion analysis revealed that deletion of oxyR abolished the induction of ahpC and katB following treatment with hydrogen peroxide or oxygen exposure. However, dps expression was induced approximately fourfold by oxygen exposure in DeltaoxyR strains but not by hydrogen peroxide. This indicates that dps expression is also under the control of an oxygen-dependent OxyR-independent mechanism. Complementation of DeltaoxyR mutant strains with wild-type oxyR and oxyR(Con) restored the inducible peroxide response and the constitutive response of the ahpCF, katB, and dps genes, respectively. However, overexpression of OxyR abolished the catalase activity but not katB expression, suggesting that higher levels of intracellular OxyR may be involved in other physiological processes. Analysis of oxyR expression in the parents and in DeltaoxyR and overexpressing oxyR strains by Northern blotting and oxyR'::xylB fusions revealed that B. fragilis OxyR does not control its own expression.

Dataset Information

Discovery and Biosynthesis of Clostyrylpyrones from the Obligate Anaerobe Clostridium roseum.

Publications

Discovery and Biosynthesis of Clostyrylpyrones from the Obligate Anaerobe <i>Clostridium roseum</i>.

Similar Datasets

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