Characterization of an Ebosin derivative produced by heterologous gene replacement in Streptomyces sp. 139.
Microb Cell Fact
; 13: 103, 2014 Jul 22.
Article
em En
| MEDLINE
| ID: mdl-25048214
ABSTRACT
BACKGROUND:
Ebosin is a novel exopolysaccharide (EPS) produced by Streptomyces sp. 139 and evidenced to possess an anti-rheumatic arthritis activity in vivo. The Ebosin biosynthesis gene cluster (ste) consists of 27 ORFs and ste7 has previously been demonstrated to code for a fucosyltransferase, which plays an essential role in the formation of repeating sugar units during Ebosin production. Aiming to generate derivatives of Ebosin for better activity, we replaced ste7 with a gene encoding for a glucosyltransferase (gtf) from Streptococcus thermophilus.RESULTS:
This alteration resulted in a novel Ebosin derivative (EPS-7 g) with its monosaccharide composition dramatically changed, especially in the proportion of glucose which increased from 1.1% (Ebosin) to 84.01% (EPS-7 g). In an ELISA analysis, EPS-7 g exhibited a higher binding activity for IL-1R, as a competitor of interleukin-1, than that of Ebosin. It also exhibited a higher inhibitory effect on the activity of IL-1ß-converting enzyme and production of IL-1ß in fibroblast-like synoviocytes (FLS). In addition, experiments with acute inflamed mice induced by croton oil showed a significantly higher anti-inflammatory activity of EPS-7 g compared with Ebosin.CONCLUSIONS:
The new Ebosin derivative EPS-7 g is more bioactive than Ebosin evaluated by a series of experiments. This is the first report demonstrating a modification of EPS structure via heterologous gene replacement in Streptomyces.
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Base de dados:
MEDLINE
Assunto principal:
Polissacarídeos Bacterianos
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Streptomyces
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Anti-Inflamatórios não Esteroides
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Família Multigênica
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Streptococcus thermophilus
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Genes Bacterianos
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article