Abstract: Described herein is a redox biosensor system for measurement of NADH/NAD+ ratio including a host strain or cell-free system including first and a second expression cassette; the first expression cassette including, in operable communication, a constitutive promoter and a gene encoding a Rex allosteric transcription factor that regulates gene expression by binding to NAD(H); and the second expression cassette including, in operable communication, a promoter regulated by the Rex allosteric transcription factor, and a gene encoding a reporter protein, wherein the first expression cassette expresses the Rex allosteric transcription factor, and, in the presence of NAD(H), the Rex allosteric transcription factor drives expression of the reporter protein from the second expression cassette, and wherein the expression of the reporter protein is proportional to the NADH/NAD+ ratio.

Abstract: In vivo screening methods for identifying inhibitors of RNA polymerase (RNAP) are provided by the present invention. In certain embodiments, methods according to the invention include steps of: (a) expressing a test RNAP in a cell containing a first reporter; (b) expressing a control RNAP in the cell of step (a) that also contains a second different reporter or, alternatively, a different cell that contains the second different reporter, wherein the first and second different reporters distinguish activities of the test and control RNAPs, respectively; (c) contacting the cell or cells of step (b) with a candidate compound; and (d) assaying to obtain a combined signal from the first reporter and second different reporter wherein a unique combined signal identifies the candidate compound as an inhibitor of an RNAP.