Ergot alkaloids and their derivatives have been traditionally used as therapeutic agents in
migraine, blood pressure regulation and help in childbirth and abortion. Their production in submerse culture is a long established biotechnological process.
Ergot alkaloids are produced mainly by members of the genus Claviceps, with Claviceps purpurea as best investigated species concerning the biochemistry of ergot
alkaloid synthesis (EAS). Genes encoding
enzymes involved in EAS have been shown to be clustered; functional analyses of EAS cluster genes have allowed to assign specific functions to several gene products. Various Claviceps species differ with respect to their host specificity and their
alkaloid content; comparison of the ergot
alkaloid clusters in these species (and of clavine
alkaloid clusters in other genera) yields interesting insights into the evolution of cluster structure. This review focuses on recently published and also yet unpublished data on the structure and evolution of the EAS gene cluster and on the function and regulation of cluster genes. These analyses have also significant biotechnological implications: the characterization of non-ribosomal
peptide synthetases (NRPS) involved in the synthesis of the
peptide moiety of ergopeptines opened interesting perspectives for the synthesis of
ergot alkaloids; on the other hand, defined mutants could be generated producing interesting intermediates or only single
peptide alkaloids (instead of the
alkaloid mixtures usually produced by industrial strains).