Heterologous production of epothilones B and D in Streptomyces venezuelae

Sung Ryeol Park, Je Won Park, Won Seok Jung, Ah Reum Han, Yeon Hee Ban, Eun Ji Kim, Jae Kyung Sohng, Sang Jun Sim, Yeo Joon Yoon

Research output: Contribution to journalArticle

27 Citations (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.

Original languageEnglish
Pages (from-to)109-117
Number of pages9
JournalApplied Microbiology and Biotechnology
Volume81
Issue number1
DOIs
Publication statusPublished - 2008 Nov 1
Externally publishedYes

Fingerprint

Streptomyces
Epothilones
Polyketides
Multigene Family
Antineoplastic Agents
Myxococcales
Polyketide Synthases
Regulator Genes
Paclitaxel
Microtubules
Cytochrome P-450 Enzyme System
Chromosomes
Peptides
desoxyepothilone B
epothilone B
Genes

Keywords

  • Epothilone
  • Heterologous production
  • Streptomyces venezuelae

ASJC Scopus subject areas

  • Biotechnology
  • Applied Microbiology and Biotechnology

Cite this

Heterologous production of epothilones B and D in Streptomyces venezuelae. / Park, Sung Ryeol; Park, Je Won; Jung, Won Seok; Han, Ah Reum; Ban, Yeon Hee; Kim, Eun Ji; Sohng, Jae Kyung; Sim, Sang Jun; Yoon, Yeo Joon.

In: Applied Microbiology and Biotechnology, Vol. 81, No. 1, 01.11.2008, p. 109-117.

Research output: Contribution to journalArticle

Park, Sung Ryeol ; Park, Je Won ; Jung, Won Seok ; Han, Ah Reum ; Ban, Yeon Hee ; Kim, Eun Ji ; Sohng, Jae Kyung ; Sim, Sang Jun ; Yoon, Yeo Joon. / Heterologous production of epothilones B and D in Streptomyces venezuelae. In: Applied Microbiology and Biotechnology. 2008 ; Vol. 81, No. 1. pp. 109-117.
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