THE GOAL OF THIS PROJECT IS TO IMPLEMENT A PROOF OF CONCEPT OF CROP STARCH BIOTRANSFORMATION INTO ANTICANCER COMPOUNDS WITH A MARINE PROTIST, THRAUSTOCHYTRIUM STRIATUM AND EVALUATION OF THE ANTICANCER EFFICACY OF THESE COMPOUNDS USING A NEW 3D MIMIC IN VIVO SYSTEM. THE OBJECTIVES ARE TO: 1) STUDY THE STARCH SACCHARIFICATION CAPACITY OF T. STRIATUM; 2) INVESTIGATE STARCH BIOCONVERSION TO ANTICANCER COMPOUNDS BY T. STRIATUM; AND 3) EXPLORE THE 3D MODEL FOR ANTICANCER ACTIVITY ANALYSIS OF THE ANTICANCER COMPOUNDS. EMERGING NEED IS CALLED FOR HIGH-VALUE OUTLETS FOR STARCHY CROPS (E.G., CORN). WE WILL SELECT WAXY, NORMAL, AND HIGH AMYLOSE CORN STARCHES TO REPRESENT STARCHES OF DIFFERENT AMYLOSE CONTENTS. WE WILL FIRST STUDY STARCH HYDROLYSIS BY THE AMYLOLYTIC ENZYMES OF T. STRIATUM, AND USE T. STRIATUM TO CONVERT STARCHES INTO ANTICANCER COMPOUNDS WHICH WILL THEN BE PURIFIED AND CHARACTERIZED. FINALLY, THE ANTICANCER EFFICACY OF THESE COMPOUNDS WILL BE ANALYZED BY USING A 3D MODEL SYSTEM WITH THE 2D MODEL AS A CONTROL FOR COMPARISON. THE SUCCESS OF THIS PROJECT WILL BE THE FIRST TO DEMONSTRATE A NEW BIOTECHNOLOGY TO CONVERT CROP STARCHES INTO ANTICANCER DRUGS WITH A MARINE PROTIST. WE EXPECT TO OBTAIN A HIGHLY PREDICTIVE 3D MODEL MIMICKING IN VIVO CONDITIONS FOR ANTICANCER DRUG PRE-SCREENING IN VITRO AT PHYSIOLOGICAL, PROTEIN AND MRNA LEVELS. THE NEW OUTLET FOR CROP STARCHES TO PRODUCE ANTICANCER DRUGS WILL INCREASE THE DOMESTIC CORN USE AND REDUCE EXPORT PRESSURE. THE STARCH-DERIVED ANTICANCER DRUGS WILL ENHANCE THE PROFITABILITY AND SUSTAINABILITY OF THE U.S. AGRICULTURE AND BIOPHARMACEUTICAL INDUSTRY.