New Strategies for Natural Products Lead Generation

Microbial sources of natural products are increasingly valued for their chemical diversity and access to biosynthetic pathways. It appears that an incredible repository of untapped microbial life and associated chemical diversity remain to be exploited. Molecular techniques such as “metagenomics” are beginning to provide access to cryptic biosynthetic pathways, which are also revealing new chemistry. Refined libraries of natural products with well-characterized components provide enhanced value as screening sources. These libraries continue to provide new chemical entities that inform biological processes and provide leads for therapeutic agents. There is a renaissance of phenotypic screening that promises to uncover numerous new links between secondary metabolites and their roles in biology. Genomic methods are growing in value as our understanding of biosynthetic processes at the molecular level expands. Screening of DNA sequences for pathways that yield particular chemistries is now a reality for certain types of biosynthetic processes, especially type I polyketide synthases and nonribosomally produced peptides. Keywords: biodiversity; marine actinomycetes; microbial genomics; natural products lead generation; natural products libraries; screening; secondary metabolites