Engineering Nonphosphorylative Metabolism for Biosynthesis

University Of Minnesota-Twin Cities, Minneapolis MN

Investigators

Abstract

1604728 Zhang, Kechun Traditionally, glycolysis and the pentose phosphate pathway are the standard metabolic routes for sugar assimilation. However, their lengthy reaction steps and complex regulation limit yield and production rate of a variety of bioproducts. The objective of this proposal is to apply metabolic engineering techniques to implement a pathway for the direct conversion of sugars into intermediates of the citric acid cycle. This will improve the carbon yield of a variety of products and improve their manufacturing processes. With higher theoretical carbon yield and shorter reaction routes than the conventional glycolysis and pentose phosphate pathways, this new non-phosphorylative metabolism has the potential for efficient biosynthesis of citric acid cycle derivatives. Although this pathway has been known for more than fifty years, the relevant enzymes remain largely unknown and uncharacterized. To enable the implementation of nonphosphorylative metabolism as a general biosynthetic platform, three specific aims will be pursued: (i) discover and evolve new gene clusters for nonphosphorylative metabolism; (ii) explore biosynthetic applications of non-phosphorylative metabolism; and (iii) co-utilize lignocellulosic feedstocks for biosynthesis. The successful realization of this project is expected to result in the fundamental understanding of a novel catabolic pathway which promises to be more efficient in many practical applications. In addition, this project will enable the processing of non-food agricultural byproducts, such as corn stover, wheat straw and citrus peel, into high-value products. The proposed new pathway will enhance the economic viability of cellulosic biorefineries which would be of significant social, environmental, and economic value. This award by the Biotechnology and Biochemical Engineering Program of the CBET Division is co-funded by the Systems and Synthetic Biology Program of the Division of Molecular and Cellular Biosciences.