Engineering plant secondary metabolite biosynthesis in microorganisms

Mattheos Koffas
Department of Chemical & Biological Engineering, 904 Furnas Hall, Buffalo NY 14260, USA

Abstract:

The goal of our group is on utilizing the richness, versatility but also simplicity of microbial organisms in order to make them ideally suited to convert cheap, renewable resources into high-value, high-quality natural products with enormous potential as nutraceuticals and pharmaceuticals.

For the purpose of reprogramming the cellular network in order to achieve optimal phenotypes supporting high-yield production, we have developed in silico models of the genome-wide metabolism of the two industrially important microorganisms, namely Escherichia coli and Saccharomyces cerevisiae. Through the application of Metabolic Flux Analysis, we can predict genetic modifications such as deletions and gene expression attenuations that lead to dramatic increases in production levels. Such Systems Biology approaches, in combination with traditional genetic engineering  have resulted in robust production levels that can result in the commercially viable processes for the synthesis of important molecules, in particular ones that belong to the plant polyphenol category. Combination of biochemical processes through the engineered microbial strains with classical mutasynthesis feeding experiments have also led to the generation of novel polyphenol molecules with promising therapeutic properties, in particular antifungal activities. Finally, our group has further developed protein engineering methodologies that allow the functional expression in prokaryotes of plant P450 monooxygenases.