Heterologous Production and Yield Improvement of Epothilones in Burkholderiales Strain DSM 7029

Research output: Contribution to journalResearch articleContributedpeer-review


  • Xiaoying Bian - , Shandong University, Helmholtz Centre for Infection Research, Saarland University (Author)
  • Biao Tang - , Fudan University (Author)
  • Yucong Yu - , Fudan University (Author)
  • Qiang Tu - , Shandong University, Helmholtz Centre for Infection Research, Saarland University (Author)
  • Frank Gross - , Chair of Applied Genomics (Author)
  • Hailong Wang - , Shandong University (Author)
  • Aiying Li - , Shandong University (Author)
  • Jun Fu - , Genetic Engineering of Stem Cells (Research Group), Shandong University (Author)
  • Yuemao Shen - , Shandong University (Author)
  • Yue-Zhong Li - , Shandong University (Author)
  • A Francis Stewart - , Chair of Applied Genomics (Author)
  • Guoping Zhao - , Fudan University, CAS - Center for Excellence in Molecular Cell Science (Author)
  • Xiaoming Ding - , Fudan University (Author)
  • Rolf Müller - , Helmholtz Centre for Infection Research, Saarland University (Author)
  • Youming Zhang - , Shandong University (Author)


The cloning of microbial natural product biosynthetic gene clusters and their heterologous expression in a suitable host have proven to be a feasible approach to improve the yield of valuable natural products and to begin mining cryptic natural products in microorganisms. Myxobacteria are a prolific source of novel bioactive natural products with only limited choices of heterologous hosts that have been exploited. Here, we describe the use of Burkholderiales strain DSM 7029 as a potential heterologous host for the functional expression of myxobacterial secondary metabolites. Using a newly established electroporation procedure, the 56 kb epothilone biosynthetic gene cluster from the myxobacterium Sorangium cellulosum was introduced into the chromosome of strain DSM 7029 by transposition. Production of epothilones A, B, C, and D was detected despite their yields being low. Optimization of the medium, introduction of the exogenous methylmalonyl-CoA biosynthetic pathway, and overexpression of rare tRNA genes resulted in an approximately 75-fold increase in the total yields of epothilones to 307 μg L -1. These results show that strain DSM 7029 has the potential to produce epothilones with reasonable titers and might be a broadly applicable host for the heterologous expression of other myxobacterial polyketide synthases and nonribosomal peptide synthetases, expediting the process of genome mining.


Original languageEnglish
Pages (from-to)1805-1812
Number of pages8
JournalACS chemical biology
Issue number7
Publication statusPublished - 21 Jul 2017

External IDs

Scopus 85025154827
ORCID /0000-0002-4754-1707/work/142248086



  • Biological Products/metabolism, Chromatography, High Pressure Liquid, Electroporation, Epothilones/biosynthesis, Industrial Microbiology/methods, Molecular Structure, Myxococcales/genetics, RNA, Transfer/genetics, Up-Regulation