Deletion of a Rare Fungal PKS CgPKS11 Promotes Chaetoglobosin A Biosynthesis, Yet Defers the Growth and Development of Chaetomium globosum.

Xudong Zhu,Xiaoran Hao,Biyun Xiang,Yanjie Liu,Guangya Shen,Qiaohong Xie

doi:10.3390/jof7090750

Xudong Zhu, Xiaoran Hao + Show 4 more

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https://doi.org/10.3390/jof7090750

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Abstract

We previously reported that chaetoglobosin A (ChA) exhibits a great potential in the biocontrol of nematodes and pathogenic fungi. To improve the production of ChA, a CRISPR-Cas9 system was created and applied for eliminating potential competitive polyketide products. One of the polyketide synthase encoding genes, Cgpks11, which is putatively involved in the biosynthesis of chaetoglocin A, was disrupted. Cgpks11 deletion led to the overexpression of the CgcheA gene cluster, which is responsible for ChA biosynthesis, and a 1.6-fold increase of ChA. Transcription of pks-1, a melanin PKS, was simultaneously upregulated. Conversely, the transcription of genes for chaetoglocin A biosynthesis, e.g., CHGG_10646 and CHGG_10649, were significantly downregulated. The deletion also led to growth retardation and seriously impaired ascospore development. This study found a novel regulatory means on the biosynthesis of ChA by CgPKS11. CgPKS11 affects chaetoglobosin A biosynthesis, growth, and development in Chaetomium globosum.

Highlights

Owing to diverse bioactivities, small molecule secondary metabolites have been major sources of medicines, promising pesticides, contaminants of food, biological probes, and targets of study for synthetic and analytical chemists [1,2]
As deletion of CgPKS11, which is responsible for the biosynthesis of chaetoglocin A, led to slower growth of the mycelium and retarded sexual development, and in particular showed a dramatic rise of chaetoglobosin A (ChA) biosynthesis
In the attempt to delete all the polyketide synthases (PKSs) in order to eliminate the possible competitive pathways in the biosynthesis of ChA, a rare type I PKS, Cgpks11, which is responsible for the biosynthesis of chaetoglocin A and lacks the acyl carrier protein (ACP) domain, was deleted

Summary

Introduction

Small molecule secondary metabolites have been major sources of medicines, promising pesticides, contaminants of food, biological probes, and targets of study for synthetic and analytical chemists [1,2]. Polyketides encompass a highly structurally diverse group of secondary products. Based on the structural organization of their functional domains, PKSs are classified into three basic categories: type I PKSs are large multifunctional proteins comprised of several functional domains and found in both bacteria and fungi; type II PKSs are formed by discrete catalytic domains and are typically found in bacteria; type III PKSs are simpler chalcone synthase-type enzymes that catalyze the formation of the product within a single active site, mainly in plants and bacteria. Modules from type I PKSs are linked to non-ribosomal peptide synthetase (NRPS) modules, which results in the production of polyketide-peptide hybrid metabolites, e.g., cytochalasans [3,5,6,7]

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