Global Regulator-Based Activation of Silent Gene Clusters

Genomics and bioinformatics analysis of genome sequences have revealed silent gene clusters that are not expressed under specific growth conditions or are undetectable at low expression levels. These silent gene clusters are called silent natural product biosynthetic gene clusters. Currently, there are two main strategies to activate these silent gene clusters. One is stochastic activation, mainly by optimizing growth conditions, adding chemical mutagens, trace metal ions, provision of exogenous small molecules, ribosome engineering, co-culture with other organisms, etc. The second is targeted activation based on genomic sequences, mainly targeting regulatory genes. Global regulators are a class of regulators that can simultaneously regulate the expression of multiple genes under specific induction conditions. In addition to epigenetic modifying enzymes, global regulators can also regulate multiple genes at the same time. Lifeasible can help customers simultaneously induce multiple gene expressions through global regulatory factors under specific environmental conditions.

Figure 1. Hyphal growth and biomass of PoLaeA-silenced strains. (Zhang G et al., 2017)

The global regulators currently used for fungal silencing gene cluster activation are listed below, including but not limited to.

• LaeA. The LaeA gene can regulate the expression of genes within multiple gene clusters simultaneously, affecting the biosynthesis of multiple fungal secondary metabolites. The regulation of fungal secondary metabolite synthases by LaeA is mainly manifested by transcriptional activation, which may regulate gene expression by altering the heterochromatin state in which the gene cluster is located.
• RsmA. RsmA is a global post-transcriptional regulator involved in regulating a variety of unrelated metabolic pathways such as carbon metabolism, motility, biofilm formation, production of virulence factors, pathogenicity, bacterial population sensing, and oxidative stress.
• CreA. CreA contains two zinc finger structures and is a significant regulator of carbon metabolism repression in filamentous fungi. CreA can be involved in the regulation of transcriptional and translational processes by binding to regulatory elements in the promoters of target genes.
• VeA. VeA acts as a global transcription factor in the synthesis of both beneficial/harmful secondary metabolites. veA can inhibit the production of toxic secondary metabolites during the growth of filamentous fungi.
• McrA. The McrA gene not only affects morphological changes in the strain but also has a function in regulating secondary metabolites.

Lifeasible can help customers target fungal modification based on gene identification and structural analysis of global transcription factors to activate silent gene clusters and regulate transcriptional expression of secondary metabolite-related genes. As your trusted partner, we can meet all your fungal phylogenetic analysis needs and provide you with efficient and high-quality services. If you want to know the details, please contact us.