Biosynthesis and control of beta-lactam antibiotics: the early steps in the "classical" tripeptide pathway

The interaction between growth and secondary metabolism develops from physiological responses of the producer organism to its environment. Nutrients are channelled into primary growth processes or into secondary processes such as antibiotic biosynthesis by a variety of metabolic controls, the nature of which has been extensively studied in organisms producing beta-lactam antibiotics via the tripeptide, delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine. In the following article we review the early stages of beta-lactam biosynthesis in fungi and actinomycetes, keeping in mind the regulation of primary pathways that provide the amino acid precursors of this group of antibiotics, as well as the regulation of the secondary pathway itself. Of special importance to organisms engaging in secondary metabolism are the control mechanisms that suppress the nonessential process during rapid growth but allow secondary metabolic genes to be expressed and resources to be diverted when environmental factors generate the appropriate biochemical signals.