Oak-Associated Negativicute Equipped with Ancestral Aromatic Polyketide Synthase Produces Antimycobacterial Dendrubins
Keishi Ishida, Gulimila Shabuer, Sebastian Schieferdecker, Sacha J Pidot, Timothy P Stinear, Uwe Knuepfer, Michael Cyrulies, Christian Hertweck
Chemistry: A European Journal | WILEY-V C H VERLAG GMBH | Published : 2020
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 a..View full abstract
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We thank A. Perner for LC HR-MS measurements, H. Heinecke for NMR measurements, C. Weigel for initial biactivity screening, and H.-M. Dahse for cytotoxicity testings. Expanded antimycobacterial assays were performed as paid service by the Institute of Microbiology and Laboratory Medicine. This study was supported by the BMBF (InfectControl). Open access funding enabled and organized by Projekt DEAL.