Predicting culture conditions for secondary metabolite production based on binding targets of biosynthetic gene cluster- specific transcription factors

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	Predicting culture conditions for secondary metabolite production based on binding targets of biosynthetic gene cluster- specific transcription factors
	FAN LU; GUO SHUHUI; CHEN RUIWEN; PARDESHI LAKHANSING; WONG KOON HO
	2024-03
Conference Name	32nd Fungal Genetics Conference
Conference Date	12/03/2024
Conference Place	Asilomar Conference Ground
Country	USA
Abstract	Fungi possess remarkable capabilities for synthesizing diverse secondary metabolites (SMs) with significant application potential in medicine, agriculture, and industry. SM biosynthetic genes are often organized in clusters on fungal genomes, where each cluster is responsible for synthesizing a specific SM. Genome sequencing has identified many novel SM biosynthetic gene clusters (BGCs) in fungi, representing a rich resource for drug discovery. However, most SM BGCs remain transcriptionally silent under standard laboratory conditions, presenting challenges for their identification. In many BGCs, a transcription factor gene is embedded within the cluster, playing a crucial role in activating other biosynthetic genes within the same cluster. However, whether these cluster- specific transcription factors can bind and regulate genes outside their cluster is not clear. We hypothesize that BGC transcription factors may regulate non-BGC genes with functions essential or favorable for the biosynthesis of the intended SM, such as metabolic reprogramming to produce necessary metabolic precursors, response to specific environmental cues, or physiologies specific for developmental stages. If this were true, it would be possible to deduce the conditions favorable for SM production based on the genome-wide targets of the BGC transcription factor for a given SM. To demonstrate this, we conducted Chromatin Immuno-Precipitation followed by Sequencing (ChIP-Seq) to map the genome-wide binding sites of AflR – the well-studied transcription factor of sterigmatocystin (ST) biosynthesis in Aspergillus nidulans. Our results revealed extensive AflR binding to genomic regions beyond the ST BGC, exerting control over numerous physiological processes. More importantly, we successfully devised specific growth conditions that promote ST production based on the AflR binding target information. Taken together, this work provides valuable insights into the regulation of ST and introduces a novel approach to activate cryptic SM BGCs, enabling the discovery of novel secondary metabolites.
Document Type	Conference paper
Collection	DEPARTMENT OF BIOMEDICAL SCIENCES
Corresponding Author	WONG KOON HO
Affiliation	Faculty of Health Sciences, University of Macau
Recommended Citation GB/T 7714	FAN LU,GUO SHUHUI,CHEN RUIWEN,et al. Predicting culture conditions for secondary metabolite production based on binding targets of biosynthetic gene cluster- specific transcription factors[C], 2024.
APA	FAN LU., GUO SHUHUI., CHEN RUIWEN., PARDESHI LAKHANSING., & WONG KOON HO (2024). Predicting culture conditions for secondary metabolite production based on binding targets of biosynthetic gene cluster- specific transcription factors. .

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