NEW YORK (GenomeWeb News) – The National Institute of General Medical Sciences plans to provide $4.5 million to fund research that will tap into genomic and metagenomic sequencing databases and use synthetic biology approaches to develop new ways to discover natural products.
NIGMS is seeking applications for projects that will use these data sets and techniques to develop new high-throughput, genome-based methods for discovering natural products, which are used to develop antibacterial and anticancer drugs, the agency said yesterday.
Natural products or organic compounds formed in nature that have already been optimized by evolutionary genetics may serve as defensive or signaling molecules, and roughly 75 percent of antibacterial and anticancer drugs are natural products, or are derived from them.
In spite of their usefulness, the process for discovering natural products has not changed much in three decades, NIGMS said. Investigators still employ a "grind and find" method that involves phenotypic screening of partially purified mixtures of compounds that were obtained from cultivable organisms.
This approach has intrinsic limitations, as it must focus on organisms that can be cultured and that provide assayable amounts of active materials, but less than 1 percent of bacteria and fungi can be cultivated and only a fraction of those produce active and useful materials, NIGMS said. These limitations have led to "a significant reduction in the rate of new discoveries," and the pool of potentially useful natural products has barely been tapped, NIGMS said.
The massive amounts of genomic and metagenomic data that is being churned out these days and recent advances in DNA cloning and other synthetic biology technologies have opened up new opportunities for using genomic information to discover natural products.
NIGMS wants to fund research that harnesses these technologies to rapidly expand the pool of natural products that are well studied and can be cultivated and used.
These multidisciplinary projects will aim to develop molecular biology and bioinformatics toolboxes for designing and assembling biosynthetic operons; model organisms for making natural products; a robust set of expression production tools; bioinformatics tools for analyzing genomic and functional data; tools for identifying and characterizing transcriptional and translational regulators; and high-throughput methods for structural characterization, among other tools.
NIGMS said it plans to fund two of these research projects in 2015.