Overexpressing transcriptional regulator in Chaetomium globosum activates a silent biosynthetic pathway: Evaluation of shanorellin biosynthesis

摘要

In recent years, many secondary metabolite gene clusters, including polyketide biosynthetic genes, have been uncovered through fungal genome sequencing. Although approximately 33 polyketide biosynthetic genes can be identified in the genome of a fungus Chaetomium globosum, only 11 fungal polyketide scaffolds can be isolated from cultures grown under typical growth conditions. Transcription factors (TFs) located within a gene cluster often determine whether its respective secondary metabolites can be biosynthesized, and it is this class of regulators that is responsible for the low expression level of biosynthetic genes and less-than-desirable yield of the corresponding natural products. Here, we explored the feasibility of activating a silent gene cluster through overexpression of a TF encoded in a putative polyketide biosynthetic gene cluster in C. globosum for which a stably propagating expression vector is unavailable.