Project description:Actinomycete genomes contain a plethora of orphan gene clusters encoding unknown secondary metabolites, and representing a huge unexploited pool of chemical diversity. The explosive increase in genome sequencing and the massive advance of bioinformatic tools have revolutionized the rationale for natural product discovery from actinomycetes. In this context, we applied a genome mining approach to discover a group of unique catecholate-hydroxamate siderophores termed as qinichelins from Streptomyces sp. MBT76. Quantitative proteomics statistically correlated a gene cluster of interest (qch) to its unknown chemotype (qinichelin), after which structural elucidation of isolated qinichelin was assisted by bioinformatics analysis and verified by MS2 and NMR experiments. Strikingly, intertwined functional crosstalk among four separately located gene clusters was implicated in the biosynthesis of qinichelins.
Project description:Microbial consortia consist of a multitude of prokaryotic and eukaryotic microorganisms. Their interaction is critical for the functioning of ecosystems. Until now, there is limited knowledge about the communication signals determining the interaction between bacteria and fungi and how they influence microbial consortia. Here, we discovered that bacterial low molecular weight arginine-derived polyketides trigger the production of distinct natural products in fungi. These compounds are produced by actinomycetes found on all continents except Antarctica and are characterized by an arginine-derived positively charged group linked to a linear or cyclic polyene moiety. Producer bacteria can be readily isolated from soil as well as fungi that decode the signal and respond with the biosynthesis of natural products. Both arginine-derived polyketides and the compounds produced by fungi in response shape microbial interactions.
Project description:Actinobacteria are a rich source of bioactive molecules, and genome sequencing has shown that the vast majority of their biosynthetic potential has yet to be explored. However, many of their biosynthetic gene clusters (BGCs) are poorly expressed in the laboratory, which prevents discovery of their cognate natural products. To exploit their full biosynthetic potential, better understanding of the signals that promote the expression of BGCs is needed. Here, we show that the human stress hormone epinephrine (adrenaline) elicits antibiotic production by Actinobacteria. Catechol was established as the likely eliciting moiety, since similar responses were seen for catechol and for the catechol-containing molecules dopamine and catechin but not for related molecules. Exploration of the catechol-responsive strain Streptomyces sp. MBT84 using mass spectral networking revealed elicitation of a BGC that produces the angucycline glycosides aquayamycin, urdamycinone B and galtamycin C. Heterologous expression of the catechol-cleaving enzymes catechol 1,2-dioxygenase or catechol 2,3 dioxygenase counteracted the eliciting effect of catechol. Thus, for the first time we show the activation of natural product biosynthesis by a human hormone, leading to the identification of the ubiquitous catechol moiety as elicitor of BGCs for siderophores and antibiotics.
Project description:Actinobacteria are a rich source of bioactive molecules, and genome sequencing has shown that the vast majority of their biosynthetic potential has yet to be explored. However, many of their biosynthetic gene clusters (BGCs) are poorly expressed in the laboratory, which prevents discovery of their cognate natural products. To exploit their full biosynthetic potential, better understanding of the signals that promote the expression of BGCs is needed. Here, we show that the human stress hormone epinephrine (adrenaline) elicits antibiotic production by Actinobacteria. Catechol was established as the likely eliciting moiety, since similar responses were seen for catechol and for the catechol-containing molecules dopamine and catechin but not for related molecules. Exploration of the catechol-responsive strain Streptomyces sp. MBT84 using mass spectral networking revealed elicitation of a BGC that produces the angucycline glycosides aquayamycin, urdamycinone B and galtamycin C. Heterologous expression of the catechol-cleaving enzymes catechol 1,2-dioxygenase or catechol 2,3 dioxygenase counteracted the eliciting effect of catechol. Thus, for the first time we show the activation of natural product biosynthesis by a human hormone, leading to the identification of the ubiquitous catechol moiety as elicitor of BGCs for siderophores and antibiotics.