title: Functional Operons in Secondary Metabolic Gene Clusters in Glarea lozoyensis (Fungi, Ascomycota, Leotiomycetes).
abstract: Operons are multigene transcriptional units which occur mostly in prokaryotes but rarely in eukaryotes. Protein-coding operons have not been reported in the Fungi even though they represent a very diverse kingdom of organisms. Here, we report a functional operon involved in the secondary metabolism of the fungus Glarea lozoyensis belonging to Leotiomycetes (Ascomycota). Two contiguous genes, glpks3 and glnrps7, encoding polyketide synthase and nonribosomal peptide synthetase, respectively, are cotranscribed into one dicistronic mRNA under the control of the same promoter, and the mRNA is then translated into two individual proteins, GLPKS3 and GLNRPS7. Heterologous expression in Aspergillus nidulans shows that the GLPKS3-GLNRPS7 enzyme complex catalyzes the biosynthesis of a novel pyrrolidinedione-containing compound, xenolozoyenone (compound 1), which indicates the operon is functional. Although it is structurally similar to prokaryotic operons, the glpks3-glnrps7 operon locus has a monophylogenic origin from fungi rather than having been horizontally transferred from prokaryotes. Moreover, two additional operons, glpks28-glnrps8 and glpks29-glnrps9, were verified at the transcriptional level in the same fungus. This is the first report of protein-coding operons in a member of the Fungi.
  
  
  OBJECTIVE
  Operons are multigene transcriptional units which occur mostly in prokaryotes but rarely in eukaryotes. Three operon-like gene structures for secondary metabolism that were discovered in the filamentous fungus Glarea lozoyensis are the first examples of protein-coding operons identified in a member of the Fungi. Among them, the glpks3-glnrps7 operon is responsible for the biosynthesis of xenolozoyenone, which is a novel tetramic acid-containing compound. Although structurally similar to prokaryotic operons, the glpks3-glnrps7 operon locus did not result from horizontal gene transfer from prokaryotes. In addition, operonlike structures have been predicted in silico to be common in other fungi. The common occurrence and operonlike structure in fungi provide evolutionary insight and essential data for eukaryotic gene transcription.
authors.forename: Qun
authors.initials: Q
authors.lastname: Yue
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Texas Therapeutics Institute, the Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Texas Therapeutics Institute, the Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Bills
authors.affiliation: State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Meichun
authors.initials: M
authors.lastname: Xiang
authors.affiliation: State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Shaojie
authors.initials: S
authors.lastname: Li
authors.affiliation: State Key Laboratory of Toxicology & Medical Countermeasures, Beijing Institute of Pharmacology & Toxicology, Beijing, China.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Che
authors.affiliation: Key Laboratory of Insect Developmental and Evolutionary Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Chengshu
authors.identifier: http://orcid.org/0000-0003-1477-1466
authors.initials: C
authors.lastname: Wang
authors.forename: Xuemei
authors.initials: X
authors.lastname: Niu
authors.affiliation: Texas Therapeutics Institute, the Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA zhiqiang.an@uth.tmc.edu liuxz@im.ac.cn.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: An
authors.affiliation: State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China zhiqiang.an@uth.tmc.edu liuxz@im.ac.cn.
authors.forename: Xingzhong
authors.initials: X
authors.lastname: Liu
mesh_terms: D001203:Ascomycota / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D001233:Aspergillus nidulans / Q000235:genetics / Q000378:metabolism; D004271:DNA, Fungal / Q000737:chemistry / Q000235:genetics; D015870:Gene Expression; D015966:Gene Expression Regulation, Fungal; D008969:Molecular Sequence Data; D005810:Multigene Family; D009876:Operon; D010453:Peptide Synthases / Q000235:genetics* / Q000378:metabolism; D048630:Polyketide Synthases / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D064210:Secondary Metabolism; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic
chemical_list: D004271:DNA, Fungal; D048630:Polyketide Synthases; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase