Kathrin Buntin

Cultivation of myxobacteria of the Nannocystis genus led to the isolation and structure elucidation of a class of novel cyclic lactone inhibitors of elongation factor 1. Whole genome sequence analysis and annotation enabled identification of the putative biosynthetic cluster and synthesis process. In biological assays the compounds displayed anti-fungal and cytotoxic activity. Combined genetic and proteomic approaches identified the eukaryotic translation elongation factor 1α (EF-1α) as the primary target for this compound class. Nannocystin A (1) displayed differential activity across various cancer cell lines and EEF1A1 expression levels appear to be the main differentiating factor. Biochemical and genetic evidence support an overlapping binding site of 1 with the anti-cancer compound didemnin B on EF-1α. This myxobacterial chemotype thus offers an interesting starting point for further investigations of the potential of therapeutics targeting elongation factor 1.

A useful strategy: Deciphering biosynthesis by trans-AT polyketide synthases (PKS) is challenging due to their highly nonlinear organization. Our analysis of the trans-AT PKS responsible for sorangicin production in the myxobacterium Sorangium cellulosum So ce12 reinforces the utility of a combined phylogenetic/retrobiosynthetic approach for understanding this complex mode of biosynthesis. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Chemistry and biology meet in the structure elucidation of the antibiotics thuggacins A–C. The absolute configuration of all stereogenic centers in the thuggacins was confirmed through a combination of chemical derivatization, NMR analysis, molecular modeling, and bioinformatic analysis of the thuggacin biosynthetic genes. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2008/z704897_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Unusual biochemistry: The pathway to the antifungal ajudazols (ajudazol A is shown) has been deduced by cloning and sequencing of the gene cluster in the myxobacterium Chondromyces crocatus, coupled with insertional mutagenesis. Ajudazol biosynthesis incorporates several unusual features, including the first P450-catalyzed dehydrogenation identified in bacterial metabolism. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2008/z705569_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.