REACTIVITY-BASED SCREENING FOR NATURAL PRODUCT DISCOVERY

摘要

A method of identifying a natural product comprising NP-[X]n is provided. The method includes several steps. The first step includes selecting an organism having a biosynthetic pathway for producing the natural product comprising NP-[X]n using a bioinformatics algorithm. The second step includes preparing a sample suspected to contain NP-[X]n including a complex cellular metabolite mixture from an organism. The third step includes reacting the sample suspected to contain NP-[X]n with reactivity probe Y according to Scheme I: Scheme I. NP-[X]n represents a natural product NP having a chemical moiety X that is susceptible to chemical modification by reactivity probe Y to form at least one product adduct NP-[X]n-m[Z]n in which chemical moiety X reacts with reactivity probe Y to form adduct Z, wherein n ranges from 1 to about 10 and m is at least 1 and m = n. The fourth step includes optionally dereplicating the product collection of at least one known labeled metabolite to provide a depleted product collection including at least one unknown labeled metabolite. The fifth step includes determining the structure of the at least one unknown labeled metabolite, thereby identifying the natural product comprising NP-[X]n.