Structure and Biosynthetic Assembly of Gulmirecins, Macrolide Antibiotics from the Predatory Bacterium Pyxidicoccus fallax

• Published in: Chemistry : a European journal Vol. 20; no. 48; pp. 15933 - 15940
• Main Authors: Schieferdecker, Sebastian, König, Stefanie, Weigel, Christiane, Dahse, Hans-Martin, Werz, Oliver, Nett, Markus
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 24-11-2014; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Subjects: Anti-Bacterial Agents - biosynthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibiotics; Assembly; Bacteria; Bacteriocins - biosynthesis; Bacteriocins - chemistry; Bacteriocins - pharmacology; Bacteriology; Biological Products - chemistry; Biomedical materials; Chemistry; Genes; Human; Humans; Hunting; Macrolides - chemistry; Macrolides - metabolism; Macrolides - pharmacology; Magnetic Resonance Spectroscopy; Methicillin-Resistant Staphylococcus aureus - drug effects; Microbial Sensitivity Tests; Molecular Sequence Data; Molecular Structure; MRSA; Multigene Family; natural products; NMR spectroscopy; polyketides; Polyketides - chemistry; Staphylococcus aureus; Staphylococcus infections; structure elucidation; natural products; structure elucidation; NMR spectroscopy; polyketides; antibiotics
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201404291

The gulmirecins constitute a new class of glycosylated macrolides that were isolated from the predatory bacterium Pyxidicoccus fallax HKI 727. Their structures were solved by a combination of NMR spectroscopic experiments and chemical derivatization. Analysis of the annotated gulmirecin gene cluster complemented the configurational assignment and provided insights into the stereochemical course of the biosynthetic assembly. The gulmirecins exhibit strong activity against staphylococci, including methicillin‐resistant Staphylococcus aureus, but no cytotoxic effects on human cells.
Molecules for hunting: Bioactivity‐guided screening of the predatory bacterium Pyxidicoccus fallax HKI 727 led to the discovery of two new macrolide antibiotics (see figure). Both compounds inhibit the growth of Gram‐positive bacteria, including methicillin‐resistant Staphylococcus aureus (MRSA), and show no cytotoxicity against human cells.