Disruption of the ste22 gene encoding a glycosyltransferase and its function in biosynthesis of Ebosin in Streptomyces sp. 139.
Streptomyces sp.139 produces an exopolysaccharide (EPS) designated Ebosin with remarkable anti-rheumatic arthritis activity in vivo. The ste (Streptomyces eps) gene cluster required for Ebosin biosynthesis has been identified. According to similarities with other proteins in the database, ste22 shows high homology with glycosyltransferases originated from different microorganisms. In this study, the ste22 gene was disrupted by double crossover via homologous recombination. The EPS produced by the mutant strain Streptomyces sp.139 (ste22(-)) has a different monosaccharide composition profile in comparison with that of Ebosin. This derivative of Ebosin retained the original antagonistic activity of IL-1R in vitro but lost the bioactivities of anti-inflammation and pain relief in vivo.
Zhang
Tianyu
T
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Peking Union Medical College, 100050 Beijing, China.
Wang
Lingyan
L
Xu
Guiyun
G
Chen
Yang
Y
Zhang
Yang
Y
Li
Yuan
Y
D018501:Antirheumatic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D017353:Gene Deletion; D016695:Glycosyltransferases / Q000235:genetics*; D008969:Molecular Sequence Data; D009005:Monosaccharides / Q000032:analysis; D005810:Multigene Family; D016254:Mutagenesis, Insertional; D011135:Polysaccharides, Bacterial / Q000096:biosynthesis* / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism*
D018501:Antirheumatic Agents; D004269:DNA, Bacterial; D009005:Monosaccharides; D011135:Polysaccharides, Bacterial; D017472:Receptors, Interleukin-1; D016695:Glycosyltransferases