Combined metabolic engineering of precursor and co-factor supply to increase α-santalene production by Saccharomyces cerevisiae

Microbial Cell Factories

Research

Michel Schalk¹  Laurent Daviet¹  Siavash Partow²  Gionata Scalcinati²  Jens Nielsen²  Verena Siewers² 

[1] Corporate R&D Division, Firmenich SA, CH-1211, Geneva, Switzerland;Department of Chemical and Biological Engineering, Chalmers University of Technology, SE-412 96, Göteborg, Sweden;

关键词: Metabolic engineering;    Isoprenoids;    Sesquiterpenes;    Continuous culture;    Saccharomyces cerevisiae;   

DOI  :  10.1186/1475-2859-11-117

 received in 2012-03-02, accepted in 2012-08-18,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundSesquiterpenes are a class of natural products with a diverse range of attractive industrial proprieties. Due to economic difficulties of sesquiterpene production via extraction from plants or chemical synthesis there is interest in developing alternative and cost efficient bioprocesses. The hydrocarbon α-santalene is a precursor of sesquiterpenes with relevant commercial applications. Here, we construct an efficient Saccharomyces cerevisiae cell factory for α-santalene production.ResultsA multistep metabolic engineering strategy targeted to increase precursor and cofactor supply was employed to manipulate the yeast metabolic network in order to redirect carbon toward the desired product. To do so, genetic modifications were introduced acting to optimize the farnesyl diphosphate branch point, modulate the mevalonate pathway, modify the ammonium assimilation pathway and enhance the activity of a transcriptional activator. The approach employed resulted in an overall α-santalene yield of a 0.0052 Cmmol (Cmmol glucose)-1 corresponding to a 4-fold improvement over the reference strain. This strategy, combined with a specifically developed continuous fermentation process, led to a final α-santalene productivity of 0.036 Cmmol (g biomass)-1 h-1.ConclusionsThe results reported in this work illustrate how the combination of a metabolic engineering strategy with fermentation technology optimization can be used to obtain significant amounts of the high-value sesquiterpene α-santalene. This represents a starting point toward the construction of a yeast “sesquiterpene factory” and for the development of an economically viable bio-based process that has the potential to replace the current production methods.

【 授权许可】

Unknown   
© Scalcinati et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.