title: Isolation and Biosynthetic Analysis of Haliamide, a New PKS-NRPS Hybrid Metabolite from the Marine Myxobacterium Haliangium ochraceum.
abstract: Myxobacteria of marine origin are rare and hard-to-culture microorganisms, but they genetically harbor high potential to produce novel antibiotics. An extensive investigation on the secondary metabolome of the unique marine myxobacterium Haliangium ochraceum SMP-2 led to the isolation of a new polyketide-nonribosomal peptide hybrid product, haliamide (1). Its structure was elucidated by spectroscopic analyses including NMR and HR-MS. Haliamide (1) showed cytotoxicity against HeLa-S3 cells with IC50 of 12 μM. Feeding experiments were performed to identify the biosynthetic building blocks of 1, revealing one benzoate, one alanine, two propionates, one acetate and one acetate-derived terminal methylene. The biosynthetic gene cluster of haliamide (hla, 21.7 kbp) was characterized through the genome mining of the producer, allowing us to establish a model for the haliamide biosynthesis. The sulfotransferase (ST)-thioesterase (TE) domains encoded in hlaB appears to be responsible for the terminal alkene formation via decarboxylation.
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan. ch3cook@gmail.com.
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan. tomura.tomohiko@a.mbox.nagoya-u.ac.jp.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Tomura
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan. john-smith-11@live.jp.
authors.forename: Junichi
authors.initials: J
authors.lastname: Sato
authors.affiliation: Institute for Innovation, Ajinomoto Co., Inc., Kawasaki, Kanagawa 210-8681, Japan. takashi_iizuka@ajinomoto.com.
authors.forename: Takashi
authors.initials: T
authors.lastname: Iizuka
authors.affiliation: R &amp; D Planning Department, Ajinomoto Co., Inc., Chuo-ku, Tokyo 104-8315, Japan. ryosuke_fudou@ajinomoto.com.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Fudou
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan. ojika@agr.nagoya-u.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ojika
mesh_terms: D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D059001:Aquatic Organisms; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D020564:Deltaproteobacteria / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D055442:Metabolome; D005810:Multigene Family; D010455:Peptides / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D061065:Polyketides / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D015238:Sulfotransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013869:Thiolester Hydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001426:Bacterial Proteins; D010455:Peptides; D061065:Polyketides; D015238:Sulfotransferases; D013869:Thiolester Hydrolases
keywords: Haliangium ochraceum; biosynthesis; haliamide; marine myxobacterium; polyketide