Actagardine is a globular lantibiotic which is stable in simulated gastric fluid and highly potent against Clostridium difficile, with reduced activity against other bacteria in the gut flora. Its derivative NVB302 has entered preclinical trial for treating C. difficile associated diarrhea. Current synthesis of actagardine derivative followed semisynthetic ways while its heterologous biosynthesis in E. coli has never been reported. We applied co-expression as an alternative and more convenient way to produce actagardine and its derivatives, with the ease of purification and substrate sequence engineering, eliminating the need of organic synthesis. Actagardine is also the only known lantipeptide possessing a sulfoxide group in its structure, introduced in vivo by GarO, the only known luciferase-like monooxygenase in all published lantipeptide biosynthesis clusters. We investigated the in vitro GarO enzymatic activity on the formation of the sulfoxide group, which will expand current knowledge on lantipeptide structures and their biosynthetic enzymes.

In vivo reconstitution and investigation of actagardine

244th National Meeting (2012)

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