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Microb Cell Fact. 2014 Jul 22;13(1):103.

Characterization of an Ebosin derivative produced by heterologous gene replacement in Streptomyces sp. 139.

Author information

  • 1Key laboratory of Biotechnology of Antibiotics, Ministry of Health, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Tian Tan, 100050, Beijing, China. e-zhangyang@163.com.
  • 2Institute of Pharmacology and Toxicology, Taiping Road, 100850, Beijing, China. shanjunjie001@126.com.
  • 3Key laboratory of Biotechnology of Antibiotics, Ministry of Health, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Tian Tan, 100050, Beijing, China. bao_yonggang@163.com.
  • 4Key laboratory of Biotechnology of Antibiotics, Ministry of Health, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Tian Tan, 100050, Beijing, China. lipingbai1973@163.com.
  • 5Key laboratory of Biotechnology of Antibiotics, Ministry of Health, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Tian Tan, 100050, Beijing, China. jr5602@163.com.
  • 6Key laboratory of Biotechnology of Antibiotics, Ministry of Health, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Tian Tan, 100050, Beijing, China. guolh5@sina.com.
  • 7Key laboratory of Biotechnology of Antibiotics, Ministry of Health, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Tian Tan, 100050, Beijing, China. yaochen3320@sina.com.
  • 8School of Biological Sciences, University of Wollongong, Wollongong, NSW, 2522, Australia. rzhang@uow.edu.au.
  • 9Key laboratory of Biotechnology of Antibiotics, Ministry of Health, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Tian Tan, 100050, Beijing, China. yuanwli@263.net.

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-1β-converting enzyme and production of IL-1β 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.

PMID:
25048214
[PubMed - as supplied by publisher]
PMCID:
PMC4347597
Free PMC Article
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