Thiamyxins: Structure and Biosynthesis of Myxobacterial RNA-Virus Inhibitors.

During our search for novel myxobacterial natural products, we discovered the thiamyxins: thiazole- and thiazoline-rich non-ribosomal peptide-polyketide hybrids with potent antiviral activity. We isolated four congeners of this unprecedented natural product family with the non-cyclized thiamyxin D fused to a glycerol unit at the C-terminus. Alongside their structure elucidation, we present a concise biosynthesis model based on biosynthetic gene cluster analysis and isotopically labelled precursor feeding.

Sesbanimide R, a Novel Cytotoxic Polyketide Produced by Magnetotactic Bacteria.

Genomic information from various magnetotactic bacteria suggested that besides their common ability to form magnetosomes, they potentially also represent a source of bioactive natural products. By using targeted deletion and transcriptional activation, we connected a large biosynthetic gene cluster (BGC) of the -acyltransferase polyketide synthase (-AT PKS) type to the biosynthesis of a novel polyketide in the alphaproteobacterium Structure elucidation by mass spectrometry and nuclear magnetic resonance spectroscopy (NMR) revealed that this secondary metabolite resembles sesbanimides, which were very recently reported from other taxa. However, sesbanimide R exhibits an additional arginine moiety the presence of which reconciles inconsistencies in the previously proposed sesbanimide biosynthesis pathway observed when comparing the chemical structure and the potential biochemistry encoded in the BGC.

In vivo and in vitro reconstitution of unique key steps in cystobactamid antibiotic biosynthesis.

Cystobactamids are myxobacteria-derived topoisomerase inhibitors with potent anti-Gram-negative activity. They are formed by a non-ribosomal peptide synthetase (NRPS) and consist of tailored para-aminobenzoic acids, connected by a unique α-methoxy-L-isoasparagine or a β-methoxy-L-asparagine linker moiety. We describe the heterologous expression of the cystobactamid biosynthetic gene cluster (BGC) in Myxococcus xanthus.

Expanding the Scope of Detectable Microbial Natural Products by Complementary Analytical Methods and Cultivation Systems.

Recent advances in genome sequencing have unveiled a large discrepancy between the genome-encoded capacity of microorganisms to produce secondary metabolites and the number detected. In this work, a two-platform mass spectrometry analysis for the comprehensive secondary metabolomics characterization of nine myxobacterial strains, focusing on extending the range of detectable secondary metabolites by diversifying analytical methods and cultivation conditions, is presented. Direct infusion measurements of crude extracts on a Fourier transform ion cyclotron resonance mass spectrometer are compared to a time-of-flight device coupled to liquid chromatography measurements.