Biotechnology-based antibiotic production

For over 50 years, antibiotic therapy has been the most important defence against microbial infections. Among industrial fermentations, antibiotic production is one of the most important sectors. The screening of natural antibiotic-producing strains has led to the production of so-called first-generation antibiotics. These micro-organisms (fungi and bacteria) are generally characterized by production that takes place only after active growth, during stress phases corresponding to morphological and physiological differentiation.

Production using non-genetically modified micro-organisms is still very low, subject to strict controls. Very early on, programs were launched to improve production by modifying strains. These programs initially involved random mutagenesis. A great deal of progress was made: elucidation of the metabolic pathways involved in antibiotic synthesis and their regulation, study of the genes involved, understanding of the resistance mechanisms of strains to the antibiotics they produce. With the development of metabolic and genetic engineering, these advances are now enabling more targeted genetic modifications. Recent techniques in directed molecular evolution have even made it possible to produce new hybrid antibiotics by recombining genes from different antibiotic-producing strains.

After a few general remarks on antibiotics and antibiotic-producing strains, this article sets out to develop the general characteristics of strain physiology, knowledge which is essential for targeted strain improvement programs and the management of production processes. The production of the desired antibiotic in purified form would require an examination of extraction and purification techniques, but this point has already been developed in the article [J 6 470] with the example of penicillin, and will therefore only be briefly recalled.

Today, most antibiotics are semi-synthetic derivatives. These so-called second- or third-generation antibiotics are produced from natural antibiotics, by chemical modifications that take into account studies of the structure-activity relationship. The aim is to improve dosage, extend the spectrum of activity and combat acquired resistance in the target micro-organisms to be eradicated. This chemical part of antibiotic production will not be developed here.