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Sponsored by the Center for Science and Technology Development of the Ministry of Education
Supervised by Ministry of Education of the People's Republic of China
In biosynthesis of natural products, potential intermediates or analogs of a particular compound in the crude extracts are commonly overlooked in routine assays due to their low concentration or because of limited structural information. This may lead into an incomplete and even an incorrect biosynthetic pathway for the target molecule. Here we established a compound-hunting approach which is based on genome mining and mass spectrometry and evaluated it to identify potential pyrrolamide compounds in the fermentation culture of Streptomyces netropsis. Several novel pyrrolamides were then detected and characterized, and a revised model for the biosynthesis of pyrrolamide compounds was proposed. Significantly, our results implied an unprecedented "iterative strategy" underlying the pyrrolamide antibiotics biosynthesis. Therefore, the approach developed in this study not only can direct scaffold-oriented discovery of potential biosynthesis intermediates and analogs, but also has the potential to extend our knowledge of existing natural product biosynthesis mechanisms.
Keywords:Microbiology & Biochemical Pharmacy; Mass spectrometry; Biosynthesis; Genome mining; Pyrrolamide