Closthioamide: An Unprecedented Polythioamide Antibiotic from the Strictly Anaerobic Bacterium Clostridium cellulolyticum

摘要

Bacteria belonging to the genus Clostridium axe among the most prominent microorganisms that lead an obligate anaerobic lifestyle. Clostridia occur in gastrointestinal tracts and are ubiquitously distributed in soil and sediments, rapidly decaying organic matter. Owing to their potent catabolic properties, interest in these organisms has grown rapidly over the past few years. Not only are Clostridia routinely employed to degrade anthropogenic cellulosic waste products, they have also been increasingly exploited to meet the need for renewable chemicals and biofuels. Although various pathogenic species produce the most powerful neurotoxins known to mankind, the tetanus and botulinum toxins, respectively, no secondary metabolites have yet been isolated from these or any other strictly anaerobic bacteria. However, bioinfor-matics analysis ("mining") of the recently sequenced genomes of Clostridium spp., for example, Clostridium kluyveri and Clostridium cellulolyticum, indicated that these bacteria harbor genes for the biosynthesis of secondary metabolites. Since the encoded cryptic natural products have been overlooked so far, it appears the biosynthesis genes remain dormant under standard laboratory conditions and are only triggered in the presence of particular stimuli. Herein we report the discovery of the first secondary metabolite, a hitherto fully unprecedented type of polythioamide, from a strictly anaerobic bacterium, Clostridium cellulolyticum.