THE INCREASED OCCURRENCES OF HERBICIDE RESISTANT WEEDS EACH YEAR INDICATE THAT OVERRELIANCE ON CHEMICAL CONTROL STRATEGIES IS REACHING A CRITICAL MOMENT. AT PRESENT, WEEDS HAVE EVOLVED RESISTANCE TO 22 OF THE 25 KNOWN HERBICIDE SITES OF ACTION. HERBICIDE RESISTANCE IS NOW REPORTED TO AFFECT 247 PLANT SPECIES WORLDWIDE. ADDED TO THIS PROBLEM IS THE LACK OF NEW CHEMISTRIES ON THE MARKET TARGETING DIFFERENT MODES OF ACTION. IN RESPONSE TO THE WORLDWIDE CONCERN OF HERBICIDE RESISTANCE IN CROPPING SYSTEMS, WE ARE DEVELOPING NEW METHODOLOGIES TO UNCOVER NOVEL COMPOUNDS ISOLATED FROM SOIL MICROORGANISMS THAT COULD BE EFFECTIVE IN WEED MANAGEMENT.THE SET OF METHODS FOCUSES ON RECOVERING SOIL SAMPLES COLLECTED FROM ROOT ZONES OF DIFFERENT AGRONOMICALLY IMPORTANT WEEDS SHOWING GROWTH INHIBITION. LARGE FRAGMENTS OF DNA ARE EXTRACTED FROM THE SOIL AND INSERTED INTO VECTORS THAT HOLD THE DNA FRAGMENTS WITHIN A HOST BACTERIAL CELL. REPLICATION OF THE BACTERIAL HOSTS PROVIDES ADDITIONAL COPIES OF THE DNA FRAGMENTS, WHICH FACILITATE HIGH THROUGHPUT SCREENING OF REGIONS OF DNA CODING FOR THE SYNTHESIS OF COMPOUNDS OF INTEREST. BACTERIA CONTAINING THE RELEVANT DNA FRAGMENTS ARE GROWN FOR COMPOUND EXTRACTION. THE COMPOUNDS ARE THEN EXAMINED USING LIQUID CHROMATOGRAPHY-MASS SPECTROMETRY AND NUCLEAR MAGNETIC RESONANCE TECHNOLOGIES FOR COMPOUND IDENTIFICATION. ONCE COMPOUNDS ARE RETESTED AND RECONFIRMED FOR WEED INHIBITION, WE ARE ABLE TO USE THE SEQUENCE STRUCTURE AS A MARKER TO SCREEN FOR SOILS HAVING THE WEED-SUPPRESSIVE COMPOUNDS. WE CAN THEN DESIGN A SET OF EXPERIMENTS TO UNDERSTAND MANAGEMENT STRATEGIES ASSOCIATED WITH THE ENRICHMENT OF THESE WEED-SUPPRESSIVE COMPOUNDS. FURTHER DOWN THE ROAD, WE HOPE TO DEVELOP MICROBIAL-BASED MANIPULATIONS OF SOILS THAT WOULD CONTROL WEEDY AND INVASIVE PLANT POPULATIONS. THE SET OF METHODOLOGIES ARE USEFUL FOR THE DEVELOPMENT OF BOTH NOVEL HERBICIDES AND COULD ALSO LEAD TO BIOLOGICAL CONTROL INVOLVING SOIL MANAGEMENT STRATEGIES THAT ENRICH FOR WEED-SUPPRESSIVE COMPOUNDS.