Oak‐Associated Negativicute Equipped with Ancestral Aromatic Polyketide Synthase Produces Antimycobacterial Dendrubins
| Autor: | Michael Cyrulies, Sebastian Schieferdecker, Keishi Ishida, Uwe Knuepfer, Sacha J. Pidot, Gulimila Shabuer, Christian Hertweck, Timothy P. Stinear |
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| Rok vydání: | 2020 |
| Předmět: |
mycobacteria
medicine.drug_class Firmicutes 010402 general chemistry Antimycobacterial 01 natural sciences Catalysis Quercus Antibiotics Phylogenetics Polyketide synthase genome mining medicine Humans Gene Phylogeny polyphenols chemistry.chemical_classification Negativicutes biology 010405 organic chemistry Communication Organic Chemistry anaerobes General Chemistry biology.organism_classification Communications Anti-Bacterial Agents 0104 chemical sciences Enzyme chemistry Biochemistry Multigene Family biology.protein Anaerobic bacteria Polyketide Synthases |
| Zdroj: | Chemistry (Weinheim an Der Bergstrasse, Germany) |
| ISSN: | 1521-3765 0947-6539 |
| DOI: | 10.1002/chem.202001939 |
| Popis: | Anaerobic bacteria have only recently been recognized as a source of antibiotics; yet, the metabolic potential of Negativicutes (Gram‐negative staining Firmicutes) such as the oak‐associated Dendrosporobacter quercicolus has remained unknown. Genome mining of D. quercicolus and phylogenetic analyses revealed a gene cluster for a type II polyketide synthase (PKS) complex that belongs to the most ancestral enzyme systems of this type. Metabolic profiling, NMR analyses, and stable‐isotope labeling led to the discovery of a new family of anthraquinone‐type polyphenols, the dendrubins, which are diversified by acylation, methylation, and dimerization. Dendrubin A and B were identified as strong antibiotics against a range of clinically relevant, human‐pathogenic mycobacteria. A path of polyketide ancestry: Genome mining revealed an ancestral type II polyketide synthase (PKS) system of the oak‐associated anaerobic bacterium Dendrosporobacter quercicolus, a member of the underexplored class of Negativicutes. Metabolic profiling led to the discovery of a new family of aromatic polyketides (dendrubins) that exhibit potent activities against a range of clinically relevant pathogenic mycobacteria (see figure). |
| Databáze: | OpenAIRE |
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