Optimizing the heterologous production of epothilone D in Myxococcus xanthus

Biotechnology and Bioengineering
Janice LauPeter J Licari

Abstract

The heterologous production of epothilone D in Myxococcus xanthus was improved by 140-fold from an initial titer of 0.16 mg/L with the incorporation of an adsorber resin, the identification of a suitable carbon source, and the implementation of a fed-batch process. To reduce the degradation of epothilone D in the basal medium, XAD-16 (20 g/L) was added to stabilize the secreted product. This greatly facilitated its recovery and enhanced the yield by three-fold. The potential of using oils as a carbon source for cell growth and product formation was also evaluated. From a screen of various oils, methyl oleate was shown to have the greatest impact. At the optimal concentration of 7 mL/L in a batch process, the maximum cell density was increased from 0.4 g dry cell weight (DCW)/L to 2 g DCW/L. Product yield, however, depended on the presence of trace elements in the production medium. With an exogenous supplement of trace metals to the basal medium, the peak epothilone D titer was enhanced eight-fold. This finding demonstrates the significant role of metal ions in cell metabolism and in epothilone biosynthesis. To further increase the product yield, a continuous fed-batch process was used to promote a higher cell density and to ma...Continue Reading

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Citations

Feb 24, 2006·Journal of Industrial Microbiology & Biotechnology·Helge B Bode, Rolf Müller
Feb 14, 2006·Journal of Industrial Microbiology & Biotechnology·Scott FrykmanPeter Licari
Jul 25, 2007·Journal of Industrial Microbiology & Biotechnology·Guo-li GongYue-zhong Li
Mar 26, 2013·Journal of Industrial Microbiology & Biotechnology·Thomas PhillipsPeter Michels
Nov 4, 2009·Journal of Natural Products·Jacob C CarlsonDavid H Sherman
Aug 17, 2002·Antimicrobial Agents and Chemotherapy·Bryan Julien, Sanjay Shah
Feb 20, 2007·Journal of Bacteriology·Aurelio Moraleda-Muñoz, Lawrence J Shimkets
May 24, 2003·Applied Microbiology and Biotechnology·R RegentinP Licari
Aug 24, 2006·Molecular Microbiology·Pamela J Bonner, Lawrence J Shimkets
Feb 7, 2004·Biotechnology Progress·Rika RegentinRuchir Desai
Oct 27, 2005·Angewandte Chemie·Helge B Bode, Rolf Müller
Jul 15, 2015·Journal of Labelled Compounds & Radiopharmaceuticals·Richard C BurrellSamuel J Bonacorsi
Aug 15, 2019·Microbial Cell Factories·Dipesh DhakalRamesh Prasad Pandey
Dec 7, 2013·Microbial Biotechnology·Shu-Guang LiYue-Zhong Li
May 9, 2009·Chemical Reviews·Gordon M CraggDavid J Newman
Oct 16, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jan ŠkubníkSilvie Rimpelová
May 10, 2013·ACS Synthetic Biology·Corina OsswaldSilke C Wenzel
Apr 19, 2019·ACS Synthetic Biology·Domen PogorevcSilke C Wenzel

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