Methods for selecting microbes from a diverse genetically modified library to detect and optimize the production of metabolites

A method of selecting a subset of microbes for the production of a metabolite comprising

• placing a population of microbes in an environment of a toxin, wherein the toxin is external to the population of microbes,
• wherein the population of microbes produces a sensor biomolecule that regulates production of an antidote to a toxin,
• wherein the population of microbes produces a metabolite binding partner of the sensor biomolecule, which binds to the sensor to induce production of the antidote in a manner dependent on the concentration of the produced metabolite,
• wherein the toxin and antidote pair is selected from the group consisting of SDS:tolC, colicin:tolC (negative selection), kanamycin:kanamycin nucleotidyltransferase, chloramphenicol:
• chloramphenicol acyl transferase, ampicillin:beta lactamase, tetracycline:tetracycline efflux pump tetA, nickel chloride:tetracycline efflux pump tetA (negative selection), and 5-fluoroorotic acid:URA3 (negative selection), and
• selecting a subset of microbes that produce sufficient metabolite to prevent microbe death.