Unlocking the trove of metabolic treasures: activating silent biosynthetic gene clusters in bacteria and fungi

Bacteria and fungi are prolific producers of secondary metabolites, yet they house a multitude of silent biosynthetic gene clusters that are poorly expressed and whose products are unknown or 'cryptic'. Stimulating the expression of these clusters and accessing their associated molecules is a major priority, as they are expected to have a veritable cornucopia of bioactivites. Here, we highlight three strategies that have been the focus of recent developments. Co-culture and elicitor screening, genetic regulator investigation and exploitation, and pathway refactoring and heterologous cluster expression, are collectively being employed to activate the expression of cryptic biosynthetic gene clusters (BGCs), and stimulate the production of novel metabolites having diverse activities.