Two decades of strain development in antibiotic-producing microorganisms (Reprinted from Developments in Industrial Microbiology, vol 7, pg 61-73, 1966)

Mutation and selection is one of the most successful methods employed for i mprovement of antibiotic yield. Indeed, the greatest single factor contribu ting to large-scale penicillin manufacture was the development of potent mo ld strains. In this, strain development was firmly established. The mutatio n-selection approach for improved yield is still predominantly employed in industrial laboratories today. During the past two decades, microbial genetics has grown from obscurity to one of the most exciting areas of biology. As a consequence, many new phil osophies and approaches are now available to industrial strain development programs. These include the application of potent new mutagens, and, for ma ny of them, a molecular basis for their action; the use of antimetabolites and the directed isolation of superior yielding variants; the incorporation of specfic analogues by mutant strains and subsequent antibiotic modificat ion; the production of structurally-modified antibiotics by mutants with sp ecific gene blocks; the selection of modified streptomycete strains followi ng phage attack; and the discovery of sexual as well as parasexual mechanis ms in actinomycetes and "imperfect" fungi. There is now speculation concern ing interspecific recombinants and the development of strains with increase d ploidy for use in qualitative and quantitative antibiotic change. These developments stress the continued importance of strain selection in t he industrial environment. Much work is necessary to make the more sophisti cated techniques flexible in the industrial laboratory. The industrial micr obiologist will have to be well trained in the concepts and practice of mic robial genetics. During the next decade, it would appear that applications of microbial genetics will play a more and more important role in industria l strain development.