RRC ID 51582
Author Sun Y, Tomura T, Sato J, Iizuka T, Fudou R, Ojika M.
Title Isolation and Biosynthetic Analysis of Haliamide, a New PKS-NRPS Hybrid Metabolite from the Marine Myxobacterium Haliangium ochraceum.
Journal Molecules
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.
Volume 21(1)
Pages 59
Published 2016-1-6
DOI 10.3390/molecules21010059
PII molecules21010059
PMID 26751435
PMC PMC6274090
MeSH Antineoplastic Agents / isolation & purification Antineoplastic Agents / metabolism* Antineoplastic Agents / pharmacology Aquatic Organisms Bacterial Proteins / chemistry Bacterial Proteins / genetics Bacterial Proteins / metabolism Cell Survival / drug effects Deltaproteobacteria / chemistry Deltaproteobacteria / genetics Deltaproteobacteria / metabolism* Gene Expression HeLa Cells Humans Inhibitory Concentration 50 Metabolome* Multigene Family Peptides / isolation & purification Peptides / metabolism* Peptides / pharmacology Polyketides / isolation & purification Polyketides / metabolism* Polyketides / pharmacology Protein Structure, Tertiary Sulfotransferases / chemistry Sulfotransferases / genetics Sulfotransferases / metabolism Thiolester Hydrolases / chemistry Thiolester Hydrolases / genetics Thiolester Hydrolases / metabolism
IF 3.06
Times Cited 17
Human and Animal Cells HeLa-S3 (SC)(RCB0271)