MANY BIOBASED PRODUCTS ARE GENERATED FROM CROP-DERIVED GLUCOSE USING LIVING MICROORGANISMS IN FERMENTATION PROCESSES. ACETYL COA IS A KEY CENTRAL METABOLITE AND AN IMPORTANT COMPONENT FOR THE SYNTHESIS OF NEW CELLS. ACETYL COA IS ALSO A PRECURSOR FOR A VERY WIDE VARIETY OF BIOCHEMICAL PRODUCTS OF COMMERCIAL INTEREST INCLUDING BUTANOL, POLY(HYDROXYALKANOATE)S, POLYKETIDES, FLAVANONES AND ISOPRENE/ISOPRENOIDS. MOST STUDIES INVOLVING SUCH PRODUCTS HAVE FOCUSED ON ENGINEERING A PATHWAY FROM ACETYL COA TO THAT SPECIFIC TARGET. IN E. COLI, THE PATHWAY OF ACETYL COA TO ACETATE HAS ALSO TYPICALLY BEEN ENGINEERED TO REDUCE THE FORMATION OF THIS BY-PRODUCT. DESPITE THE FACT THAT NEARLY TWO-THIRDS OF ACETYL COA IN E. COLI IS DIRECTED THROUGH THE ENZYME CITRATE SYNTHASE, LITTLE WORK HAS FOCUSED ON INCREASING THE POOL OF ACETYL COA BY REDUCING THE ACTIVITY OF CITRATE SYNTHASE. THIS PROJECT WILL INVESTIGATE APPROACHES TO MODULATE BUT NOT ELIMINATE THE ACTIVITY OF CITRATE SYNTHASE, THEREBY OFFERING A MEANS TO DIRECT MORE GLUCOSE TOWARD ACETYL COA-DERIVED PRODUCTS. THE FOCUS WILL BE ON TWO MODEL COMPOUNDS, CITRAMALATE AND ACETONE, WHICH REPRESENT TWO CLASSES OF COMPOUNDS DERIVED FROM ACETYL COA. PURIFICATION OF CITRAMALATE WILL ALLOW THE EXAMINATION OF ITS PROPERTIES AS AN AGRICULTURALLY-DERIVED COMPONENT IN BIODEGRADABLE POLYMERS. THE PROPOSED GENERAL APPROACH TO REDIRECT CENTRAL METABOLISM TOWARD A DESIRED PRODUCT IN A TUNABLE AND OPTIMAL WAY WILL EXPAND THE UTILIZATION OF AGRICULTURAL MATERIALS AND ALLOW BROADER EXPLOITATION OF DESIRABLE OPERATIONAL STRATEGIES (E.G., FED-BATCH, CONTINUOUS FERMENTATION) WHICH IMPROVE YIELD AND PRODUCTIVITY FOR A VAST ARRAY OF BIOBASED PRODUCTS.
$488,290FY2018National Institute of Food and AgricultureUSDA
University Of Georgia Research Foundation, Inc.