Exploring Secondary Metabolism of Bacteria, Fungi and Plants – Emerging JGI Core Competencies for User Science
Secondary metabolites are those molecules produced by organisms that are not required for growth per se, but which provide significant advantages to those organisms producing them. These molecules are synthesized in response to environmental cues and facilitate nutrient acquisition, defense mechanisms against predatory organisms, communication between symbiotic and mutual hosts, and the ability to resist toxic compounds. Thus, identifying secondary metabolites and understanding their biosynthesis and roles in the environment can enable both new routes to bio-based molecules and also new methods to improve bioenergy crop yields. Genes responsible for production of these secondary metabolites are often clustered in their genomes to form biosynthetic gene clusters (BGCs) which contain all genes required for biosynthesis of precursors, assembly of the compound scaffold, tailoring of the scaffold, and often additional genes for resistance, export, and regulation. Even in bacteria, only 10 to 20% of secondary metabolite BGCs are expressed when organisms are grown in isolation under standard laboratory conditions. Therefore, a tremendous amount of biochemical diversity remains untapped. The expertise and capabilities that the JGI has to explore bacteria, fungi, and plants will position the JGI to functionally explore the diversity of secondary metabolites across these organisms, and expand the repertoire of secondary metabolites and the tools for characterizing them.
Exploring Opportunities in Secondary Metabolite Research
The JGI has established a Secondary Metabolites Group, led by JGI Director Nigel Mouncey, to identify and pursue opportunities associated with secondary metabolite discovery and characterization. In addition to Director Mouncey, the Secondary Metabolites Group includes Hiroshi Otani, Syliva Kunakom, and Dan Udwary who, in addition to his research contributions, is host of the JGI podcast, Natural Prodcast. Already the JGI has initiated several targeted efforts addressing the following grand challenges.
Integrating JGI Capabilities for Exploring Earth’s Secondary Metabolome
Among the initiatives being pursued by the JGI is the Earth’s Secondary Metabolome Project. By bringing together capabilities to systematically explore novel secondary metabolites and their biosynthesis, using state-of-the-art workflows that integrate large-scale bioinformatic mining, DNA synthesis, metabolomics, high-performance computing, chemoinformatics, and bioassays promises to expand our understanding of these important molecules and their roles in biochemical processes on the planet. Related to this project, the JGI supports, through the Community Science Program, an outreach partnership with Tiny Earth, a network of instructors and students focused on student-sourcing antibiotic discovery from soil.