Abstract
BackgroundMicrobial secondary metabolism is regulated by a complex and mostly-unknown network of global and pathway-specific regulators. A dozen biosynthetic gene clusters for secondary metabolites have been reported in myxobacteria, but a few regulation factors have been identified.ResultsWe identified a transcription regulator Esi for the biosynthesis of epothilones. Inactivation of esi promoted the epothilone production, while overexpression of the gene suppressed the production. The regulation was determined to be resulted from the transcriptional changes of epothilone genes. Esi was able to bind, probably via the N-terminus of the protein, to an inverted repeat sequence in the promoter of the epothilone biosynthetic gene cluster. The Esi-homologous sequences retrieved from the RefSeq database are all of the Proteobacteria. However, the Esi regulation is not universal in myxobacteria, because the esi gene exists only in a few myxobacterial genomes.ConclusionsEsi binds to the epothilone promoter and down-regulates the transcriptional level of the whole gene cluster to affect the biosynthesis of epothilone. This is the first transcription regulator identified for epothilone biosynthesis.
Highlights
Microbial secondary metabolism is regulated by a complex and mostly-unknown network of global and pathway-specific regulators
We reported the identification of a negative transcription regulator for the biosynthesis of epothilones
Inactivation of esi promotes the epothilone production in S. cellulosum So0157‐2 Using the conjugation and subsequent homologous recombination protocols as previously described [38], we inactivated genes flanking the epothilone gene cluster in S. cellulosum So0157-2 to determine whether they were associated with the synthesis, regulation or modification of epothilones
Summary
Microbial secondary metabolism is regulated by a complex and mostly-unknown network of global and pathway-specific regulators. A dozen biosynthetic gene clusters for secondary metabolites have been reported in myxobacteria, but a few regulation factors have been identified. The production of secondary metabolites in microorganisms is normally limited, probably due to the complex and mostly-unknown network of global and pathway-specific regulators, as well as the large biosynthetic gene cluster containing many gene modules [1,2,3,4]. A dozen gene clusters for the biosynthesis of secondary metabolites have been reported in Epothilones are originally produced by some strains of S. cellulosum, and are a group of antitumor compounds mimicking paclitaxel in the polymerization of tubulin [6, 12].
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