Drug synthesis by genetically engineered microorganisms.

The interplay between chemical and biological approaches to drug discovery and development is increasing with the advent of combinatorial methods that accelerate the output of screening programs and the development of genetically modified microorganisms able to make new metabolites and larger amounts of known ones. Actinomycetes, the most prolific microbial source of known drugs, can produce new aromatic compounds by manipulation of the Type II polyketide synthase genes as well as analogs of existing macrolide antibiotics, unavailable by chemical synthesis, through targeted mutation of specific biosynthetic genes. Genetic alteration of pathways to aminoglycoside and oligopeptide antibiotics should offer equally promising approaches to manufacturing novel metabolites. When coupled with DNA-based prescreening of microbial isolates for genes associated with known pharmacologically active agents, these new genetic-based approaches are creating an expanded role for microorganisms in drug research.