- Reconstitution of Iterative Thioamidation in Closthioamide Biosynthesis Reveals Tailoring Strategy for Nonribosomal Peptide Backbones
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Thioamide-containing nonribosomal peptides (NRPs) are exceedingly rare. Recently the biosynthetic gene cluster for the thioamidated NRP antibiotic closthioamide (CTA) was reported, however, the enzyme responsible for and the timing of thioamide formation remained enigmatic. Here, genome editing, biochemical assays, and mutational studies are used to demonstrate that an Fe-S cluster containing member of the adenine nucleotide α-hydrolase protein superfamily (CtaC) is responsible for sulfur incorporation during CTA biosynthesis. However, unlike all previously characterized members, CtaC functions in a thiotemplated manner. In addition to prompting a revision of the CTA biosynthetic pathway, the reconstitution of CtaC provides the first example of a NRP thioamide synthetase. Finally, CtaC is used as a bioinformatic handle to demonstrate that thioamidated NRP biosynthetic gene clusters are more widespread than previously appreciated.
- Dunbar, Kyle L.,Dell, Maria,Molloy, Evelyn M.,Kloss, Florian,Hertweck, Christian
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- Sustainable Synthesis of Balsalazide and Sulfasalazine Based on Diazotization with Low Concentrations of Nitrogen Dioxide in Air
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Low concentrations of nitrogen dioxide, which arises as a side product from a range of industrial processes, can effectively be recycled through the diazotization of anilines. The studies reported herein now demonstrate that the removal of nitrogen dioxide from gas streams is even more effective when hydrophilic anilines are used as starting materials. The diazonium salts, which are obtained in this way in up to quantitative yields, can directly be employed in azo coupling reactions, thus opening up an attractive route to the industrially important group of azo compounds.
- Hofmann, Dagmar,Gans, Eva,Krüll, Jasmin,Heinrich, Markus R.
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supporting information
p. 4042 - 4045
(2017/03/31)
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- CLOSTHIOAMIDES
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This invention relates to the field of biologically active compounds and specifically to closthioamides, pharmaceutical compositions comprising these compounds, and their use as antibiotic, antifungal, and/or cytotoxic agent.
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- Highly efficient total synthesis of the clostridium-derived anti-MRSA antibiotic closthioamide
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The antibiotic closthioamide from Clostridium cellulolyticum, the first example of a secondary metabolite from strictly anaerobic bacteria, was synthesized by a versatile and highly efficient synthetic route. This starts from simple building blocks and involves convergent peptide coupling and polythionation. The antibiotic closthioamide from Clostridium cellulolyticum, the first example of a secondary metabolite from strictly anaerobic bacteria, was synthesized by a versatile and highly efficient route starting from simple building blocks, involving convergent peptide coupling and polythionation. Copyright
- Kloss, Florian,Lincke, Thorger,Hertweck, Christian
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supporting information; experimental part
p. 1429 - 1431
(2011/04/25)
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