2 - β-Lactam-Producing Microorganisms: Their Biology and Fermentation Behavior

Abstract

This chapter provides an overview of β-lactam producing microorganisms and their molecular biology and the fermentation behavior. Mutation and genetic recombination have played important roles in the fermentation development of penicillin and cephalosporin antibiotics. The low productivity of the original strain of Penicillin chrysogenum and Cephalosporium acremonium led to an exploitation of the genetic potential of beneficial mutations to generate super-productive commercial strains of these β-lactam producing fungi. The successful preservation during long-term storage of high-yielding mutant strains used for the commercial manufacture of penicillins and cephalosporins is essential for a successful industrial fermentation process. Ideally, preservation procedures must provide conditions in which mutant strains are preserved for long periods of time, free from phenotypic changes with respect to uniform high production of the desired metabolic product. The development and control of fermentation processes for the major commercial antibiotic fermentations for penicillin G or V and cephalosporin C has attracted the attention of fermentation microbiologists and biochemical engineers. The increased interest stems from the fact that microbiologists and biochemists have better insight into the metabolic regulation of secondary metabolite fermentations. The discovery of efficient transformation of yeast, the availability of cloning vectors in yeast, and the discovery of promoters in yeast now make it possible for the transferral of yeast hybrid plasmids to fungi producing penicillins or cephalosporins by transformation of protoplasts.