Insights into microbial cryptic gene activation and strain improvement: principle, application and technical aspects.

As bacteria and fungi have been found to contain genes encoding enzymes that synthesize a plethora of potential secondary metabolites, interest has grown in the activation of these cryptic pathways. Homologous and heterologous expression of these cryptic secondary metabolite-biosynthetic genes, often silent under ordinary laboratory fermentation conditions, may lead to the discovery of novel secondary metabolites. This review addresses current progress in the activation of these pathways, describing methods for activating silent genes. It especially focuses on genetic manipulation of transcription and translation (ribosome engineering), the utilization of elicitors, metabolism remodeling and co-cultivation. In particular, the principles and technical points of ribosome engineering and the significance of S-adenosylmethionine in bacterial physiology, especially secondary metabolism, are described in detail.