title: Effects of nitrogen metabolism on growth and aflatoxin biosynthesis in Aspergillus flavus.
abstract: Aflatoxins (AFs), produced mainly by Aspergillus flavus and Aspergillus parasiticus, are strongly toxic and carcinogenic. Here, we showed that glutamine is the optimal nitrogen source for AF-production in A. flavus grown in Czapek Dox medium. Additionally, 4mM glutamine was the threshold for high production of aflatoxin B1. However, no significant impact of glutamine synthetase inhibitor was detected for on AF biosynthesis. In contrast, rapamycin could significantly suppress the glutamine inducing effect on AFs production, simultaneously inhibiting the fungal growth and conidiation. To identify the genes and regulatory networks involved in AFs biosynthesis, especially concerning the nitrogen source metabolism pathway and the target of rapamycin (TOR) signaling pathway, we obtained transcriptomes for A. flavus under treatment of three nitrogen sources by RNA-sequencing. We identified 1429 differentially expressed genes. Through GO and KEGG pathway analyses, the relationship between nitrogen metabolism and AFs biosynthesis was revealed, and the effects of TOR inhibitor were confirmed. Additionally, the quantitative real-time PCR results verified the credibility and reliability of the RNA-seq data, and were consistent with the other experimental results. Our research laid the foundation for a primary study on the involvement of the nitrogen regulatory network and TOR signaling pathway in AF biosynthesis.
authors.affiliation: Key Laboratory of Pathogenic Fungi and Mycotoxins of Fujian Province, Key Laboratory of Biopesticide and Chemical Biology of Education Ministry, School of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Key Laboratory of Pathogenic Fungi and Mycotoxins of Fujian Province, Key Laboratory of Biopesticide and Chemical Biology of Education Ministry, School of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China. Electronic address: 15980692732@163.com.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Han
authors.affiliation: Key Laboratory of Pathogenic Fungi and Mycotoxins of Fujian Province, Key Laboratory of Biopesticide and Chemical Biology of Education Ministry, School of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China.
authors.forename: Youhuang
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Department of Biology, Saint Louis University, St. Louis, MO 63103, United States.
authors.forename: Zhenguo
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Key Laboratory of Pathogenic Fungi and Mycotoxins of Fujian Province, Key Laboratory of Biopesticide and Chemical Biology of Education Ministry, School of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China.
authors.forename: Mengguang
authors.initials: M
authors.lastname: Qiu
authors.affiliation: Key Laboratory of Pathogenic Fungi and Mycotoxins of Fujian Province, Key Laboratory of Biopesticide and Chemical Biology of Education Ministry, School of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Nie
authors.affiliation: Key Laboratory of Pathogenic Fungi and Mycotoxins of Fujian Province, Key Laboratory of Biopesticide and Chemical Biology of Education Ministry, School of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Wang
authors.affiliation: Key Laboratory of Pathogenic Fungi and Mycotoxins of Fujian Province, Key Laboratory of Biopesticide and Chemical Biology of Education Ministry, School of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Pathogenic Fungi and Mycotoxins of Fujian Province, Key Laboratory of Biopesticide and Chemical Biology of Education Ministry, School of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China.
authors.forename: Zhenhong
authors.initials: Z
authors.lastname: Zhuang
authors.affiliation: Key Laboratory of Pathogenic Fungi and Mycotoxins of Fujian Province, Key Laboratory of Biopesticide and Chemical Biology of Education Ministry, School of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Key Laboratory of Pathogenic Fungi and Mycotoxins of Fujian Province, Key Laboratory of Biopesticide and Chemical Biology of Education Ministry, School of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China. Electronic address: wshyyl@sina.com.
authors.forename: Shihua
authors.initials: S
authors.lastname: Wang
mesh_terms: D016604:Aflatoxin B1 / Q000096:biosynthesis*; D001231:Aspergillus flavus / Q000187:drug effects / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks / Q000187:drug effects; D005974:Glutamate-Ammonia Ligase / Q000037:antagonists & inhibitors / Q000235:genetics; D005973:Glutamine / Q000378:metabolism*; D009584:Nitrogen / Q000378:metabolism*; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D059467:Transcriptome / Q000187:drug effects
chemical_list: D005973:Glutamine; D016604:Aflatoxin B1; D058570:TOR Serine-Threonine Kinases; D005974:Glutamate-Ammonia Ligase; D009584:Nitrogen; D020123:Sirolimus
keywords: Aflatoxins; Aspergillus flavus; Glutamine; Nitrogen sources; RNA-seq