Glucose limited feed strategy leads to increased production of fusicocca-2,10(14)-diene by Saccharomyces cerevisiae

AMB Express

Lisa Marie Halka¹  Kevin Koenen¹  Alica Kleinschmidt¹  Rolf Wichmann¹  Christian Nowacki² 

[1] Laboratory of Biochemical Engineering, Department of Biochemical and Chemical Engineering, TU Dortmund University;Laboratory of Bioprocess Engineering, Department of Biochemical and Chemical Engineering, TU Dortmund University;

关键词: Fusicocca-2,10(14)-diene;    Fed-batch fermentation;    Feed strategy;    Model of feed control;    Production improvement;    Potential of process development;   

DOI  :  10.1186/s13568-018-0662-8

来源: DOAJ

【 摘 要 】

Abstract Fusicocca-2,10(14)-diene (FCdiene) is a diterpene which is interesting as a precursor of the anti-cancer drug fusicoccin A and therefore for pharmaceutical applications. Production of FCdiene using a genetically modified Saccharomyces cerevisiae has been previously demonstrated with batch cultivations with a product concentration up to 10 mg/L. However, it is widely known that fed-batch processes can significantly improve product titer in yeast fermentations. This study focuses on the establishment of fed-batch fermentation for FCdiene production because fed-batch cultivations using FeedBeads® indicated that limiting glucose supply could increase yields of biomass (1.07 gCDW/gGlucose instead of 0.20 gCDW/gGlucose) and FCdiene (21.54 mgFCdiene/gGlucose instead of 9.74 mgFCdiene/gGlucose) in shake flask scale and may have implications for larger scale processes. We implemented a new exponential glucose feed profile in a 1.8 L stirred tank reactor. This reduced overfeeding and the consequent, ethanol production. As a result improvements in cell concentrations up to 246% could be achieved and FCdiene yield increased up to 2.8X in the first 28 h. FCdiene concentration reached 161 mg/L and 320 mg/L at 44 h. Fed-batch and batch mode were combined to examine dynamics of bi-modal cultivation where a fed-batch phase was used for biomass production and a batch phase used for FCdiene production potentially supported by ethanol consumption as reported on production of betulinic acid. The present study highlights the potential of process development improvements which increase high-value heterologous diterpene yields from S. cerevisiae.

【 授权许可】

Unknown