The Natural Product Biosynthesis (NatPro) was established in July 2011 with the funding of a contract from the National Institute of General Medical Sciences (NIH) entitled Enzyme Discovery for Natural Product Biosynthesis. The goals of NatPro are to apply technologies developed by the Protein Structure Initiative (PSI) to problems of interest to the community of biologists and biochemists who investigate the role of natural products in human health and disease.
The NatPro will play strong joint roles in both the identification of new natural product pathways and the subsequent discovery of new natural product-based pharmaceuticals by revealing the structures and active sites of novel enzymes, characterizing the enzymatic reactions of the gene products, identifying new natural products, and thus offering opportunities to identify and customize the pathways by altering specificities and/or identifying novel proteins or domains with desired enzymatic properties.
Natural products and their derivatives continue to play an important role in the drug pipeline. Over time, 7000 known structures have led to more than 20 commercial drugs, and about half of the new drugs approved in the last decade are based on natural products. Screening of new natural products and their analogs will continue, and be enhanced by modern methods such as metabolic engineering, synthetic biology, and structural analysis of compounds and the enzymes that produce them. For example, new biosynthetic routes are being built around engineered systems such as the modular polyketide synthases to produce new compounds.
There are also still a tremendous number of new microbial natural products to be explored, as evidenced by the genomic sequencing data coming forth. Nevertheless, the discovery of new compounds remains an adventitious endeavor. Genome mining efforts to identify interesting clusters and to predict what natural products might come from these clusters of genes are beginning to produce hypotheses, however, the homology of the enzymes to known enzymes is generally low.
Enzyme Discovery for Natural Product Biosynthesis is supported by NIH/NIGMS grant number U01GM098248.