New Nocobactin Derivatives with Antimuscarinic Activity, Terpenibactins A–C, Revealed by Genome Mining of Nocardia terpenica IFM 0406

We report a genomics‐guided exploration of the metabolic potential of the brasilicardin producer strain Nocardia terpenica IFM 0406. Bioinformatics analysis of the whole genome sequence revealed the presence of a biosynthetic gene cluster presumably responsible for the generation of formerly unknown...

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Published in:Chembiochem : a European journal of chemical biology 2020-08, Vol.21 (15), p.2205-2213
Main Authors: Chen, Julia, Frediansyah, Andri, Männle, Daniel, Straetener, Jan, Brötz‐Oesterhelt, Heike, Ziemert, Nadine, Kaysser, Leonard, Gross, Harald
Format: Article
Language:English
Subjects:
Acetylcholine receptors (muscarinic)
Bioinformatics
Cytotoxicity
Derivatives
Genomes
Mass spectrometry
Mass spectroscopy
Nocardia
Nucleotide sequence
Siderophores
Toxicity
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Summary:We report a genomics‐guided exploration of the metabolic potential of the brasilicardin producer strain Nocardia terpenica IFM 0406. Bioinformatics analysis of the whole genome sequence revealed the presence of a biosynthetic gene cluster presumably responsible for the generation of formerly unknown nocobactin derivatives. Mass spectrometry‐assisted isolation led to the identification of three new siderophores, terpenibactins A (1), B (2) and C (3), which belong to the class of nocobactins. Their structures were elucidated by employing spectroscopic techniques. Compounds 1–3 demonstrated inhibitory activity towards the muscarinic M3 receptor, while exhibiting only a low cytotoxicity. Nature's combinatorial biosynthesis produces new bioactive nocobactin derivatives. Genome mining led to the discovery and characterization of terpenibactins A−C, three new nocobactins from the bacterium Nocardia terpenica IFM 0406 that exhibit unprecedented combinations of asteroidic acid, lipid and modified lysine residues. They demonstrate low cytotoxicity but potent inhibitory activity towards the muscarinic M3 receptor.
ISSN:1439-4227
1439-7633
DOI:10.1002/cbic.202000062