Chapter 9 - Cryptic Pathways and Implications for Novel Drug Discovery

Abstract

The bacterial taxa that produce the largest number of chemically diverse secondary metabolites include the members of the order Actinomycetales, especially the streptomycetes, and soil bacilli, myxococci, and pseudomonads. In addition, fungi produce 42% of known antibiotics. 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 chapter addresses current progress in the activation of these pathways, describing methods for activating silent genes, especially focusing on genetic manipulation of transcription, and translation (ribosome engineering), the utilization of elicitors, metabolism remodeling, and cocultivation.