Co-cultivation strategies to induce de novo synthesis of novel chemical scaffolds from cryptic secondary metabolite gene clusters

Abstract

Recent developments in genomic mining have revealed that many microbes possess the huge potential to produce structurally diverse secondary metabolites of industrial and therapeutic use. Many microbial gene clusters have been identified to be cryptic or orphan or silent under standard laboratory growth conditions. In the last few years, several tools and techniques have been developed to trigger/induce these cryptic/silent/orphan biosynthetic pathways. In addition to the tools that require prior understanding of the gene sequences of the studied microbes, several other tools and techniques have been designed, independent to genome or genome sequences. One of the approaches is a “co-culturing” which involves the cultivation of two (or more) microbes (interspecies interactions) in the same closed and restricted environment. Microbial co-cultures can be seen as the natural communities where they interact with each other through cell to cell contact or signaling molecules. Such interactions lead to the induction of valuable chemical scaffolds (secondary metabolites/natural products) which may escort to the novel drug discovery. The present chapter emphasizes on the co-culture strategies involving fungus-fungus and fungus-bacterium interactions that lead to the production of diverse metabolite structures from otherwise cryptic/silent/orphan biosynthetic gene clusters. The various strategies, highlighting variable methods of performing intra-and interspecies co-culture experiments and the biological activities as well as diversity of thus produced metabolites, are presented.