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Heterologous production of epothilones B and D in Streptomyces venezuelae

Title
Heterologous production of epothilones B and D in Streptomyces venezuelae
Authors
Park S.R.Park J.W.Jung W.S.Han A.R.Ban Y.-H.Kim E.J.Sohng J.K.Sim S.J.Yoon Y.J.
Ewha Authors
윤여준
SCOPUS Author ID
윤여준scopus
Issue Date
2008
Journal Title
Applied Microbiology and Biotechnology
ISSN
0175-7598JCR Link
Citation
vol. 81, no. 1, pp. 109 - 117
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Epothilones, produced from the myxobacterium Sorangium cellulosum, are potential anticancer agents that stabilize microtubules in a similar manner to paclitaxel. The entire epothilone biosynthetic gene cluster was heterologously expressed in an engineered strain of Streptomyces venezuelae bearing a deletion of pikromycin polyketide synthase gene cluster. The resulting strains produced approximately 0.1 μg/l of epothilone B as a sole product after 4 days cultivation. Deletion of an epoF encoding the cytochrome P450 epoxidase gave rise to a mutant that selectively produces 0.4 μg/l of epothilone D. To increase the production level of epothilones B and D, an additional copy of the positive regulatory gene pikD was introduced into the chromosome of both S. venezuleae mutant strains. The resulting strains showed enhanced production of corresponding compounds (approximately 2-fold). However, deletion of putative transport genes, orf3 and orf14 in the epothilone D producing S. venezuelae mutant strain, led to an approximately 3-fold reduction in epothilone D production. These results introduce S. venezuelae as an alternative heterologous host for the production of these valuable anticancer agents and demonstrate the possibility of engineering this strain as a generic heterologous host for the production of polyketides and hybrid polyketide-nonribosomal peptides. © 2008 Springer-Verlag.
DOI
10.1007/s00253-008-1674-0
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자연과학대학 > 화학·나노과학전공 > Journal papers
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