Engineering antibiotic producers to overcome the limitations of classical strain improvement programs

Improvement of the antibiotic yield of industrial strains is invariably the main target of industry-oriented research. The approaches used in the past were rational selection, extensive mutagenesis, and biochemical screening. These approaches have their limitations, which are likely to be overcome by the judicious application of recombinant DNA techniques. Efficient cloning vectors and transformation systems have now become available even for antibiotic producers that were previously difficult to manipulate genetically. The genes responsible for antibiotic biosynthesis can now be easily isolated and manipulated. In the first half of this review article, the limitations of classical strain improvement programs and the development of recombinant DNA techniques for cloning and analyzing genes responsible for antibiotic biosynthesis are discussed. The second half of this article addresses some of the major achievements, including the development of genetically engineered microbes, especially with reference to beta-lactams, anthracyclines, and rifamycins.