报告题目：Natural Products 2.0: From Genome to Drug
报 告 人：高江涛 福建农林大学 教授
联 系 人：冯雁 firstname.lastname@example.org
报告摘要：Although natural products have been a particularly rich source of human medicines, activity-based or chemistry-based screening results in a very high rate of rediscovery of known molecules. Based on the large number of natural product biosynthetic genes in microbial genomes, many have proposed “genome mining” as an alternative approach for discovery efforts; however, this idea has yet to be performed experimentally on a large scale. Here, we demonstrate the feasibility of large-scale, high-throughput genome mining by screening a collection of over 10,000 actinomycetes for the genetic potential to make phosphonic acids, a class of natural products with diverse and useful bioactivities. Genome sequencing identified a diverse collection of phosphonate biosynthetic gene clusters within 278 strains. Characterization of strains within five of these groups resulted in the discovery of 11 previously undescribed phosphonic acid natural products. Analysis of the genome sequences from the remaining strains suggests that the majority of the phosphonate biosynthetic repertoire of Actinobacteria has been captured at the gene level. This dereplicated strain collection now provides a reservoir of numerous, as yet undiscovered, phosphonate natural products.