A synthetic biology platform for the discovery and commercialization of natural products.

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Specialized metabolites (also known as natural products) are naturally-occurring molecules made by environmental microorganisms that have potent biological activities. Some are beneficial: penicillin, vancomycin, amphoteracin and tetracycline are used as antibiotics to fight bacterial and fungal infections. Conversely, some are harmful. An example is aflatoxin, a potentially fatal toxin produced by food-contaminating Aspergillus species and the causative agent of liver damage and cancer. This proposal concerns specialized metabolites that are of shared interest between the Nodwell laboratory and Toronto Research Chemicals: aflatoxin and pepticinnamin. The Nodwell laboratory is developing pepticinnamin as an anti fungal drug; Toronto Research Chemicals needs a source of aflatoxin to serve as a standard in portable detection kits for aflatoxin. The major limitation in this area of research and commercialization is that the specialized metabolites tend to be produced in very small amounts by the microbes that make them. The molecules themselves are usually too complicated to produce synthetically so this is a major road block. The purpose of this collaborative effort between the Nodwell lab and Toronto Research Chemicals is to overcome this road block by developing methods for producing these molecules at very high levels. To this end we will develop strategies for optimizing the biosynthetic genes for these molecules for higher level expression in living cells. We will engineer these optimized genes into "chassis" strains designed for controlled gene expression. Finally we will develop industrial-scale culture conditions for producing each molecule at a scale appropriate for our research and commercialization needs. This is an initial focus: we regard this work on aflatoxin and pepticinnamin as a trial effort in which we will generate a platform that we can apply to many other compounds of shared mutual interest in the years to come. Our hope is that this will lead to ongoing collaboration.