Engineering Nonphosphorylative Metabolism to Biosynthesize TCA Cycle Derivatives

Biosynthesis of various important platform chemicals and biofuels involves the intermediates of the tricarboxylic acid (TCA) cycle. In most microorganisms, conversion of sugars such as glucose and xylose into these TCA cycle intermediates requires lengthy reaction steps (~14 steps) with complex regulations, making optimization of these biosynthetic pathways very challenging and time-consuming. We have developed a strategy to engineer nonphosphorylative metabolism to convert sugars directly into TCA cycle intermediates in less than six steps. We have used this shortcut pathway to develop simplified routes for the TCA derivatives such as glutamate, glutaconate and 1,4-butanediol.  This work enables the processing of non-food agricultural by-products into high-value chemicals using novel metabolic pathways.