title: Identification of the Fluvirucin B2 (Sch 38518) Biosynthetic Gene Cluster from Actinomadura fulva subsp. indica ATCC 53714: substrate Specificity of the β-Amino Acid Selective Adenylating Enzyme FlvN.
abstract: Fluvirucins are 14-membered macrolactam polyketides that show antifungal and antivirus activities. Fluvirucins have the β-alanine starter unit at their polyketide skeletons. To understand the construction mechanism of the β-alanine moiety in fluvirucin biosyntheses, we have identified the biosynthetic cluster of fluvirucin B2 produced from Actinomadura fulva subsp. indica ATCC 53714. The identified gene cluster contains three polyketide synthases, four characteristic β-amino acid-carrying enzymes, one decarboxylase, and one amidohydrolase. We next investigated the activity of the adenylation enzyme FlvN, which is a key enzyme for the selective incorporation of a β-amino acid substrate. FlvN showed strong preference for l-aspartate over other amino acids such as β-alanine. Based on these results, we propose a biosynthetic pathway for fluvirucin B2.
authors.affiliation: a Department of Chemistry , Tokyo Institute of Technology , Tokyo , Japan.
authors.forename: Akimasa
authors.initials: A
authors.lastname: Miyanaga
authors.affiliation: b Department of Chemistry and Materials Science , Tokyo Institute of Technology , Tokyo , Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hayakawa
authors.affiliation: a Department of Chemistry , Tokyo Institute of Technology , Tokyo , Japan.
authors.forename: Mario
authors.initials: M
authors.lastname: Numakura
authors.affiliation: c Japan Biological Informatics Consortium , Tokyo , Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Hashimoto
authors.affiliation: d Okinawa Biotechnology Business Support Center , Okinawa Institute of Advanced Sciences , Uruma , Japan.
authors.forename: Kuniko
authors.initials: K
authors.lastname: Teruya
authors.affiliation: d Okinawa Biotechnology Business Support Center , Okinawa Institute of Advanced Sciences , Uruma , Japan.|e Okinawa Biotechnology Business Support Center , Okinawa Science and Technology Promotion Center , Uruma , Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Hirano
authors.affiliation: f National Institute of Advanced Industrial Science and Technology , Tokyo , Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Shin-Ya
authors.affiliation: a Department of Chemistry , Tokyo Institute of Technology , Tokyo , Japan.
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Kudo
authors.affiliation: b Department of Chemistry and Materials Science , Tokyo Institute of Technology , Tokyo , Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Eguchi
mesh_terms: D039903:Actinobacteria / Q000201:enzymology / Q000235:genetics*; D000249:Adenosine Monophosphate / Q000378:metabolism; D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism; D000890:Anti-Infective Agents / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002262:Carboxy-Lyases / Q000235:genetics / Q000378:metabolism; D003001:Cloning, Molecular; D003837:Deoxy Sugars / Q000096:biosynthesis* / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D015964:Gene Expression Regulation, Bacterial; D016680:Genome, Bacterial; D007769:Lactams; D058977:Molecular Sequence Annotation; D005810:Multigene Family; D048630:Polyketide Synthases / Q000235:genetics / Q000378:metabolism; D061065:Polyketides / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D015091:beta-Alanine / Q000378:metabolism*
chemical_list: D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D003837:Deoxy Sugars; D007769:Lactams; D061065:Polyketides; D011994:Recombinant Proteins; C094360:fluvirucin B2; D015091:beta-Alanine; D000249:Adenosine Monophosphate; D048630:Polyketide Synthases; D000581:Amidohydrolases; D002262:Carboxy-Lyases
keywords: adenylation enzyme; fluvirucin; genome mining; macrolactam antibiotics; polyketide