A metagenomic strategy for harnessing the chemical repertoire of the human microbiome

• DOI: 10.1126/science.aax9176
• Publication Date: 2019-10-03T23:05:14Z
• Authors: Yuki Sugimoto; Francine R. Camacho; Shuo Wang; Pranatchareeya Ch...; Arman Odabas; Abhishek Biswas; Philip D. Jeffrey; Mohamed S. Donia
• Keywords: 0301 basic medicine; 03 medical and health sciences; Host Microbial Interactions; 13. Climate action; Microbiota; Multigene Family; Polyketides; Humans; Metagenome; Metagenomics; 3. Good health

Prospecting for drugs in the microbiome

The microbiome is an important source of natural products that can profoundly influence health and disease in the host. Sugimoto et al. constructed a modular, probabilistic strategy called MetaBGC to uncover biosynthetic gene clusters (BGCs) in human microbiome samples (see the Perspective by Henke and Clardy). The authors found geographic and strain-specific distributions of BGCs. By zeroing in on two type II aromatic polyketides, the native organisms were identified, the BGCs were reconstructed in Streptomyces , and the products were characterized. When expressed in Bacillus subtilis , the products resembled currently used anticancer drugs and antibiotics. These polyketides were not cytotoxic but had inhibitory activity against oral Gram-positive bacteria, which may reflect the niche and ecology of the originating organisms.

Science , this issue p. eaax9176 ; see also p. 1309