Systematically activation of secondary metabolic biosynthetic gene clusters and investigating their regulation in Aspergillus nidulans.

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	Systematically activation of secondary metabolic biosynthetic gene clusters and investigating their regulation in Aspergillus nidulans.
	Guo, S.; Qin, L.; Dong, L.; Tan, K.; Wong, K. H.
	2018-06-08
Source Publication	5th Macau Symposium on Biomedical Sciences 2018
Abstract	Natural products are the source of more than half of the drugs currently used in the clinics. Secondary metabolites (SMs), which are an important class of natural products produced mainly by plant, filamentous fungi and bacteria, have diverse chemical structures and many useful bioactivities. Intriguingly, genes required for SMs production are often co-located in clusters (termed as Biosynthetic Gene Clusters (BGCs)) in the genome of producing organisms. It is believed that the cluster arrangement is to facilitate co-regulation of biosynthetic genes at the levels of chromatin and transcription. Approximately 1424 BGCs from different kingdoms have been annotated in 2017. In filamentous fungi, which is well known for rich SM resources, genome mining has predicted many more previously unaware BGCs, but these novel BGCs are not expressed under lab culture conditions and remain to be discovered. Based on the regulation pattern of a few known BGCs, we hypothesized that silent BGCs could be activated to produce specific compounds by overexpressing cluster-specific transcription factors (TFs) that usually reside within respective BGCs. We first initiated a proof of principle pilot experiment involving over-expression of twelve SM TFs of Aspergillus nidulans using an extremely strong xylose-inducible promoter and obtained encouraging supports to the hypothesis. I then systematically created 50 strains each over-expressing one specific TF. Preliminary growth analysis shows that most of the strains produced visible colorful pigments, which is usually an indication of SM production, specifically under inducing condition. Fermentation metabolites from four strains show significant anti-bacteria activity to both S.aureus and B.subtilis. Chromatin ImmunoPrecipitation sequencing (ChIP-seq) of twelve overexpressed TFs have been performed so far, and genome-wide analysis revealed three BGCs clearly activated by overexpressed respective TFs with one of them being a novel BGC. Systematic characterization for all 50 strains, BGC regulation and compound identification for activated clusters are all in progress. The project will provide in-depth understanding about SM regulation in filamentous fungi and discover novel BGC and compounds.
Keyword	secondary metabolites aspergillus nidulans gene clusters
Language	英語English
The Source to Article	PB_Publication
PUB ID	37726
Document Type	Conference paper
Collection	DEPARTMENT OF BIOMEDICAL SCIENCES Faculty of Health Sciences
Corresponding Author	Wong, K. H.
Recommended Citation GB/T 7714	Guo, S.,Qin, L.,Dong, L.,et al. Systematically activation of secondary metabolic biosynthetic gene clusters and investigating their regulation in Aspergillus nidulans.[C], 2018.
APA	Guo, S.., Qin, L.., Dong, L.., Tan, K.., & Wong, K. H. (2018). Systematically activation of secondary metabolic biosynthetic gene clusters and investigating their regulation in Aspergillus nidulans.. 5th Macau Symposium on Biomedical Sciences 2018.

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