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Heterologous expression of tylosin polyketide synthase and production of a hybrid bioactive macrolide in Streptomyces venezuelae

Title
Heterologous expression of tylosin polyketide synthase and production of a hybrid bioactive macrolide in Streptomyces venezuelae
Authors
Jung W.S.Lee S.K.Hong J.S.J.Park S.R.Jeong S.J.Han A.R.Sohng J.K.Kim B.G.Choi C.Y.Sherman D.H.Yoon Y.J.
Ewha Authors
윤여준
SCOPUS Author ID
윤여준scopus
Issue Date
2006
Journal Title
Applied Microbiology and Biotechnology
ISSN
0175-7598JCR Link
Citation
vol. 72, no. 4, pp. 763 - 769
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Tylosin polyketide synthase (Tyl PKS) was heterologously expressed in an engineered strain of Streptomyces venezuelae bearing a deletion of pikromycin PKS gene cluster using two compatible low-copy plasmids, each under the control of a pikAI promoter. The mutant strain produced 0.5 mg/l of the 16-membered ring macrolactone, tylactone, after a 4-day culture, which is a considerably reduced culture period to reach the maximum production level compared to other Streptomyces hosts. To improve the production level of tylactone, several precursors for ethylmalonyl-CoA were fed to the growing medium, leading to a 2.8-fold improvement (1.4 mg/ml); however, switching the pikAI promoter to an actI promoter had no observable effect. In addition, a small amount of desosamine-glycosylated tylactone was detected from the extract of the mutant strain, revealing that the native glycosyltransferase DesVII displayed relaxed substrate specificity in accepting the 16-membered ring macrolactone to produce the glycosylated tylactone. These results demonstrate a successful attempt for a heterologous expression of Tyl PKS in S. venezuelae and introduce S. venezuelae as a rapid heterologous expression system for the production of secondary metabolites. © 2006 Springer-Verlag.
DOI
10.1007/s00253-006-0318-5
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자연과학대학 > 화학·나노과학전공 > Journal papers
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