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Biological Chemistry

Glycogenomics Debuts

Mass spec and genome mining team up to identify biosynthetic pathways that make sugar-linked natural products

by Celia Henry Arnaud
November 11, 2013 | APPEARED IN VOLUME 91, ISSUE 45

Sugar-containing microbial natural products are rich sources of potential drugs. But the vast array of glycosylation (sugar-addition) pathways makes characterizing previously unknown glycosylated natural products difficult. To speed up characterization, Pieter C. Dorrestein, Bradley S. Moore, and coworkers at the University of California, San Diego, combine mass spectrometry and genome mining in a method they call “glycogenomics” (Proc. Natl. Acad. Sci. USA 2013, DOI: 10.1073/pnas.1315492110). First, they established a “glycogenetic code” by calculating MS fragmentation patterns for sugars commonly found in microbial glycosylated natural products. This glycogenetic code allows them to link the chemical signatures to glycosylation genes in sequenced microbial genomes. Because the genes that code for the various parts of a glycosylated natural product usually cluster together, the chemical signatures allow the researchers to quickly home in on candidate biosynthetic pathways. They used the method to identify biosynthetic pathways responsible for several bioactive glycosylated natural products, including the anticancer agent cinerubin B and the antibiotic arenimycin B.

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