Abstract: The invention is directed to methods and compositions for the determination of deoxyxylulose 5-phosphate synthase (DXPS) activity. The methods and compositions of the invention are amenable to high-throughput screening assays for the identification of inhibitors and enhancers of DXPS activity. Such compounds have use in the modulation of plant and microbial growth. The compositions of the invention are DXPS fragments and chimeric polypeptides that have increased solubility as compared to the wild-type DXPS polypeptide. These DXPS fragments and chimeric polypeptides can be recombinantly expressed and purified in quantities suitable for high-throughput screening assays. The assays of the invention are based on the detection of substrates of DXPS that remain after a DXPS reaction.