New lantibiotics from cyanobacteria

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http://urn.fi/URN:NBN:fi:hulib-201606092355
Title: New lantibiotics from cyanobacteria
Author: Yang, Jiahui Jr
Contributor: University of Helsinki, Faculty of Agriculture and Forestry, Department of Food and Environmental Sciences
Publisher: Helsingfors universitet
Date: 2016
Language: eng
URI: http://urn.fi/URN:NBN:fi:hulib-201606092355
http://hdl.handle.net/10138/163737
Thesis level: master's thesis
Discipline: Mikrobiologi
Microbiology
Mikrobiologia
Abstract: Lantibiotics are a subgroup of bacteriocins, produced by Gram-positive bacteria to inhibit the growth of closely related strains. They are used as food preservatives e.g. nisin, and some are in clinical trials, e.g. duramycin A and microbisporicin. Cinnamycin is a 19 amino acid lantibiotic that inhibits the growth of Gram-positive rods. Recent work suggests that cyanobacteria might be able to make variants of cinnamycin. Here I determined the product of a cinnamycin biosynthetic pathway present in the genomes of a benthic cyanobacteria. The genome mining analysis demonstrated that three cyanobacterial strains and seven actinobacterial strains contained the genes responsible for the production of cinnamycin. Cinnamycin variants were detected from cyanobacteria Oscillatoria sp. PCC 10802 and actinobacteria Streptomyces roseoverticillatus DSM 40845, respectively. Oscillatoria sp. PCC 10802 produced a cinnamycin variant named oscillamycin, with mass of 1966.86 Da. Stable nitrogen (15N) and sulphur (34S) isotope labeling of the cyanobacterium indicated that the oscillamycin contains 3 sulfur atoms and 23 nitrogen atoms. However, the mass of oscillamycin was 16 units bigger than the bioinformatic predictions. LC-MS analysis suggested that the oscillamycin contains a hydroxyl-proline in addition to hydroxyl aspartic acid. The oscillamycin gene cluster was cloned and successfully expressed in Escherichia coli BL21. Small amounts of oscillamycin (0.25 µg) were purified from Oscillatoria sp. PCC 10802 and showed tentative antimicrobial activity against Bacillus subtilis HAMBI 251. This study demonstrated that cyanobacteria and actinobacteria share a lantibiotic gene cluster and that the lantibiotic produced differed in just four amino acids. The phylogenetic analysis suggested that the cinnamycin gene cluster was transferred from actinobacteria to cyanobacteria by an ancient horizontal gene transfer event. This study expands the chemical diversity of cinnamycin variants. This is the first report of a lantibiotic from cyanobacteria suggesting that cyanobacteria might be a novel source of antibiotics, which could be useful in addressing the antibiotic resistance issue.
Subject: Oscillatoria sp.
genome mining
cyanobacteria
lantibiotics
cinnamycin


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