Engineered and total biosynthesis of fungal specialized metabolites

Abstract

Filamentous fungi produce a very wide range of complex and often bioactive metabolites, demonstrating their inherent ability as hosts of complex biosynthetic pathways. Recent advances in molecular sciences related to fungi have afforded the development of new tools that allow the rational total biosynthesis of highly complex specialized metabolites in a single process. Increasingly, these pathways can also be engineered to produce new metabolites. Engineering can be at the level of gene deletion, gene addition, formation of mixed pathways, engineering of scaffold synthases and engineering of tailoring enzymes. Combination of these approaches with hosts that can metabolize low-value waste streams opens the prospect of one-step syntheses from garbage. The total biosynthesis and engineering of complex natural products is now routinely achieved in filamentous fungal host organisms. This technology offers substantial advantages over traditional total chemical synthesis for the production of both known and new specialized metabolites.