title: Putative methyltransferase LaeA and transcription factor CreA are necessary for proper asexual development and controlling secondary metabolic gene cluster expression.
abstract: The morphological development of fungi is a complex process and is often coupled with secondary metabolite production. In this study, we assessed the function of putative methyltransferase LaeA and transcription factor CreA in controlling asexual development and secondary metabolic gene cluster expression in Penicillium oxalicum. The deletion of laeA (ΔlaeA) impaired the conidiation in P. oxalicum, with a downregulated expression of brlA. Overexpression of P. oxalicum brlA in ΔlaeA could upregulate brlA and abaA remarkably, but could not rescue the conidiation defect; therefore, brlA and abaA expression were necessary but not sufficient for conidiation. Deletion of creA in ΔlaeA background (ΔlaeAΔcreA) blocked conidiation with a white fluffy phenotype. Nutrient-rich medium could not rescue developmental defects in ΔlaeAΔcreA mutant but could rescue defects in ΔlaeA. Expression of 10 genes, namely, albA/wA, abrB/yA, arpA, aygA, arpA-like, arpB, arpB-like, rodA, rodA-like, and rodB, for pigmentation and spore wall protein genes was silenced in ΔlaeAΔcreA, whereas only six of them were downregulated in ΔlaeA. Among the 28 secondary metabolism gene clusters in P. oxalicum, four secondary metabolism gene clusters were silenced in ΔlaeA and two were also silenced in ΔbrlA mutant. A total of 10 physically linked and coregulated genes were distributed over five chromosomes in ΔlaeA. Six of these genes were located in subtelomeric regions, thus demonstrating a positional bias for LaeA-regulated clusters toward subtelomeric regions. All of silenced clusters located in subtelomeric regions were derepressed in ΔlaeAΔcreA, hence showing that lack of CreA could remediate the repression of gene clusters in ΔlaeA background. Results show that both putative methyltransferase LaeA and transcription factor CreA are necessary for proper asexual development and controlling secondary metabolic gene cluster expression.
authors.affiliation: National Glycoengineering Research Center and State Key Lab of Microbial Technology, Shandong University, Jinan 250100, China; Shandong Provincial Key Laboratory of Carbohydrate Chemistry and Glycobiology, Shandong University, Jinan 250100, China. Electronic address: 1219464954@qq.com.
authors.forename: Xiujun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: National Glycoengineering Research Center and State Key Lab of Microbial Technology, Shandong University, Jinan 250100, China. Electronic address: 345859686@qq.com.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: National Glycoengineering Research Center and State Key Lab of Microbial Technology, Shandong University, Jinan 250100, China. Electronic address: 791126532@qq.com.
authors.forename: Longfei
authors.initials: L
authors.lastname: Bao
authors.affiliation: National Glycoengineering Research Center and State Key Lab of Microbial Technology, Shandong University, Jinan 250100, China. Electronic address: 1780530986@qq.com.
authors.forename: Liwei
authors.initials: L
authors.lastname: Gao
authors.affiliation: National Glycoengineering Research Center and State Key Lab of Microbial Technology, Shandong University, Jinan 250100, China. Electronic address: ygshan@126.com.
authors.forename: Guangshan
authors.initials: G
authors.lastname: Yao
authors.affiliation: National Glycoengineering Research Center and State Key Lab of Microbial Technology, Shandong University, Jinan 250100, China; Shandong Provincial Key Laboratory of Carbohydrate Chemistry and Glycobiology, Shandong University, Jinan 250100, China. Electronic address: 780882131@qq.com.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Mathematics, Shandong University, Jinan 250100, China. Electronic address: yzf199108@163.com.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Yang
authors.affiliation: National Glycoengineering Research Center and State Key Lab of Microbial Technology, Shandong University, Jinan 250100, China. Electronic address: lzhlzh@vip.126.com.
authors.forename: Zhonghai
authors.initials: Z
authors.lastname: Li
authors.affiliation: National Glycoengineering Research Center and State Key Lab of Microbial Technology, Shandong University, Jinan 250100, China. Electronic address: zhongyaohua@sdu.edu.cn.
authors.forename: Yaohua
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Key Laboratory of Biofuels, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao 266101, China. Electronic address: lifl@qibebt.ac.cn.
authors.forename: Fuli
authors.initials: F
authors.lastname: Li
authors.affiliation: Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China. Electronic address: yinheng@dicp.ac.cn.
authors.forename: Heng
authors.initials: H
authors.lastname: Yin
authors.affiliation: National Glycoengineering Research Center and State Key Lab of Microbial Technology, Shandong University, Jinan 250100, China. Electronic address: quyinbo@sdu.edu.cn.
authors.forename: Yinbo
authors.initials: Y
authors.lastname: Qu
authors.affiliation: National Glycoengineering Research Center and State Key Lab of Microbial Technology, Shandong University, Jinan 250100, China; Shandong Provincial Key Laboratory of Carbohydrate Chemistry and Glycobiology, Shandong University, Jinan 250100, China. Electronic address: qinyuqi@sdu.edu.cn.
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Qin
mesh_terms: D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D056229:Fungal Structures; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D020868:Gene Silencing; D005800:Genes, Fungal; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D005810:Multigene Family; D009154:Mutation; D010407:Penicillium / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D005656:Fungal Proteins; D014157:Transcription Factors; D008780:Methyltransferases
keywords: Asexual development; CreA; LaeA; Penicillium oxalicum; Secondary metabolism