Introduction to engineering the biosynthesis of fungal natural products

Filamentous fungi are highly diverse eukaryotes that inhabit all known ecosystems on earth. Estimates suggest that more than 2 × 10⁶ species are likely to exist, and analyses of typical fungal genomes suggest they harbour around 50 biosynthetic gene clusters on average. The biosynthetic potential of these organisms is thus vast. Fungi produce all the main classes of secondary metabolites, and numerous hybrid compounds. Many are highly useful in medicine such as the ‘classic’ special metabolites penicillins, cephalosporins, statins and mycophenolic acid, and new antimicrobial agents such as the pleuromutilins and enfumafungins that overcome specific patterns of resistance. Fungi differentiated from bacteria more than a billion years ago, so there has been plenty of time for uniquely fungal biosynthetic systems to evolve.