title: 4-Hydroxybenzoic acid is a diffusible factor that connects metabolic shikimate pathway to the biosynthesis of a unique antifungal metabolite in Lysobacter enzymogenes.
abstract: Heat-stable antifungal factor (HSAF) produced by Lysobacter enzymogenes is a potential lead compound for developing new antibiotics. Yet, how L. enzymogenes regulates the HSAF biosynthesis remains largely unknown. Here, we show that 4-hydroxybenzoic acid (4-HBA) serves as a diffusible factor for regulating HSAF biosynthesis. The biosynthesis of 4-HBA involved an oxygenase, LenB2, and mutation of lenB2 almost completely abolished 4-HBA production, leading to significantly impaired HSAF production. Introduction of a heterologous gene coding for 4-HBA biosynthetic enzyme into the lenB2 mutant restored the production of 4-HBA and HSAF to their corresponding wild-type levels. Exogenous addition of 0.5-1 μM 4-HBA was sufficient to restore HSAF production in the lenB2 mutant. Furthermore, the shikimate pathway was found to regulate the biosynthesis of HSAF via 4-HBA. Finally, we identified a LysR-family transcription factor (LysRLe) with activity directed to HSAF production. LysRLecould bind to the HSAF promoter and, as a result, regulates expression of HSAF biosynthesis genes. The 4-HBA could bind to LysRLeand appeared to partly enhance formation of the LysRLe-DNA complex.Collectively, our findings suggest that L. enzymogenes produces 4-HBA to serve as an adaptor molecule to link the shikimate pathway to the biosynthesis of a unique antifungal metabolite (HSAF).
authors.affiliation: Department of Plant Pathology, College of Plant Protection, Nanjing Agricultural University, Key Laboratory of Integrated Management of Crop Diseases and Pests (Nanjing Agricultural University), Ministry of Education Nanjing, 210095, People's Republic of China.
authors.forename: Zhenhe
authors.initials: Z
authors.lastname: Su
authors.affiliation: Department of Plant Pathology, College of Plant Protection, Nanjing Agricultural University, Key Laboratory of Integrated Management of Crop Diseases and Pests (Nanjing Agricultural University), Ministry of Education Nanjing, 210095, People's Republic of China.
authors.forename: Hongfu
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Plant Pathology, College of Plant Protection, Nanjing Agricultural University, Key Laboratory of Integrated Management of Crop Diseases and Pests (Nanjing Agricultural University), Ministry of Education Nanjing, 210095, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE, 68588.
authors.forename: Simon
authors.initials: S
authors.lastname: Tombosa
authors.affiliation: Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE, 68588.
authors.forename: Liangcheng
authors.initials: L
authors.lastname: Du
authors.affiliation: Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE, 68588.|Department of Natural Products, Key Laboratory of Chemical Biology, School of Pharmaceutical Sciences, Shandong University, Jinan, 250100, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Natural Products, Key Laboratory of Chemical Biology, School of Pharmaceutical Sciences, Shandong University, Jinan, 250100, People's Republic of China.
authors.forename: Yuemao
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Plant Pathology, College of Plant Protection, Nanjing Agricultural University, Key Laboratory of Integrated Management of Crop Diseases and Pests (Nanjing Agricultural University), Ministry of Education Nanjing, 210095, People's Republic of China.
authors.forename: Guoliang
authors.identifier: 0000-0003-3577-3241
authors.initials: G
authors.lastname: Qian
authors.affiliation: Department of Plant Pathology, College of Plant Protection, Nanjing Agricultural University, Key Laboratory of Integrated Management of Crop Diseases and Pests (Nanjing Agricultural University), Ministry of Education Nanjing, 210095, People's Republic of China.|Department of Plant Pathology, Institute of Plant Protection, Jiangsu Academy of Agricultural Sciences, Nanjing, 210014, People's Republic of China.
authors.forename: Fengquan
authors.initials: F
authors.lastname: Liu
mesh_terms: D000935:Antifungal Agents / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism; D002087:Butyrates / Q000378:metabolism; D053528:Lysobacter / Q000235:genetics / Q000378:metabolism*; D053858:Metabolic Networks and Pathways; D010226:Parabens / Q000378:metabolism*; D012765:Shikimic Acid / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C459561:4-(1-(4-hydroxyphenyl)-2-phenylbuten-1-yl)phenoxy-n-butyric acid; D000935:Antifungal Agents; D001426:Bacterial Proteins; D002087:Butyrates; D010226:Parabens; D014157:Transcription Factors; D012765:Shikimic Acid; C038193:4-hydroxybenzoic acid