A MYST Histone Acetyltransferase Modulates Conidia Development and Secondary Metabolism in Pestalotiopsis microspora, a Taxol Producer

Qian Zhang,Longfei Chen,Dan Wang,Xudong Zhu,Oren Akhberdi,Heng Liu,Dongsheng Wei,Xiaoran Hao

doi:10.1038/s41598-018-25983-8

Qian Zhang, Longfei Chen + Show 6 more

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https://doi.org/10.1038/s41598-018-25983-8

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Journal: Scientific Reports	Publication Date: May 29, 2018
Citations: 9	License type: open-access

Affiliation: Nankai University, Beijing Normal University

Abstract

Reverse genetics is a promising strategy for elucidating the regulatory mechanisms involved in secondary metabolism and development in fungi. Previous studies have demonstrated the key role of histone acetyltransferases in transcriptional regulation. Here, we identified a MYST family histone acetyltransferase encoding gene, mst2, in the filamentous fungus Pestalotiopsis microspora NK17 and revealed its role in development and secondary metabolism. The gene mst2 showed temporal expression that corresponded to the conidiation process in the wild-type strain. Deletion of mst2 resulted in serious growth retardation and impaired conidial development, e.g., a delay and reduced capacity of conidiation and aberrant conidia. Overexpression of mst2 triggered earlier conidiation and higher conidial production. Additionally, deletion of mst2 led to abnormal germination of the conidia and caused cell wall defects. Most significantly, by HPLC profiling, we found that loss of mst2 diminished the production of secondary metabolites in the fungus. Our data suggest that mst2 may function as a general mediator in growth, secondary metabolism and morphological development.

Highlights

The chromatin structure of eukaryotic chromosomes plays a fundamental role in the control of gene expression[9,10]
As one of our goals is to understand the biosynthesis of secondary metabolites (SMs) in this fungus, we have created a mutant library with the strategy of genome-wide mutagenesis by Agrobacterium tumefaciens-mediated insertion of the T-DNA in NK1719,20
A series of BLAST searches using MYST domain sequences revealed that NK17 has three genes, GME6965_g, GME8786_g and GME6006_g, with high similarity to histone acetyltransferase (HAT) in the MYST family, which were designated mst[1], mst[2] and mst[3], respectively

Summary

Introduction

The chromatin structure of eukaryotic chromosomes plays a fundamental role in the control of gene expression[9,10]. The endophytic fungus P. microspora NK17 was recently isolated by our laboratory as a producer of a Taxol-like molecule[18] In addition to another interesting small polyketide, pestalotiollide B, which is structurally analogous to the inhibitor of cholesterol ester transfer protein (CETP), dibenzodioxocinones were recently isolated from cultures of this strain[19]. We identified the disrupted gene, which encoded a HAT of the MYST family (Moz-Ybf2/Sas3-Sas2-Tip60) and was designated mst[2] in the study (there are three homologues in the genome). Articles on the function of MYST family HATs in filamentous fungi are scarce, fungal genome sequencing projects suggest that they are widely present in the kingdom. We describe here some important functions of MYST family member mst[2] in P. microspora NK17, including its critical roles in the development of conidia, fungicide resistance and the biosynthesis of secondary metabolites. Complementation of mst[2] could restore this defective phenotype (right panels)

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