Activation of Silent Gene Clusters in Aspergillus nidulans using Hybrid Transcription Factors.

C.A. Rabot, M. Grau, C.C. Wang

Author address: 

Pharmacology & Pharmaceutical Sciences, University of Southern California, Los Angeles, CA.

Abstract: 

 Fungal secondary metabolites (SMs) represent a largely underexploited source of clinically and agriculturally useful compounds. Bioinformatic analyses of fungal genomes suggest that the number of putative biosynthetic gene clusters far exceeds the number of known SMs. However, around 70% of these putative gene clusters are silent under standard laboratory conditions. Over the past few decades, many groups have employed a number of different strategies to activate these silent gene clusters, such as varying growth conditions, promoter replacement, co-culturing with other species, or epigenetic modifications. One additional strategy to activate these gene clusters is to manipulate the expression of transcriptional regulators. Previous work in our laboratory has shown that placing the transcription factor of a given gene cluster under the control of an inducible promoter can be a successful strategy to induce or increase expression of a cryptic gene cluster. However, some gene clusters were not activated when this approach was taken, suggesting the need for an improved strategy to induce the expression of gene clusters of interest. The focus of this project is to generate hybrid transcription factors to activate a silent gene clusters. This was accomplished by maintaining the native DNA-binding domain, but replacing the native activation domain of a transcription factor with one that is more efficient in the recruitment of the transcriptional machinery necessary for transcribing a given gene. Preliminary data from this project, in which hybrid transcription factors were generated for three putative gene clusters in Aspergillus nidulans, suggests that this approach is successful in turning on silent gene clusters

2019

abstract No: 

595F

Full conference title: 

30th Fungal Genetics Conference 2019
    • Fungal Genetics Conference 30th (2019)