Combined metabolic engineering of precursor and co-factor supply to increase α-santalene production by Saccharomyces cerevisiae
Journal article, 2012

Background Sesquiterpenes 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. Results A 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. Conclusions The 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.

Saccharomyces cerevisiae

Metabolic engineering

Isoprenoids

Sesquiterpenes

Continuous culture

Author

Gionata Scalcinati

Chalmers, Chemical and Biological Engineering, Life Sciences

Siavash Partow

Chalmers, Chemical and Biological Engineering, Life Sciences

Verena Siewers

Chalmers, Chemical and Biological Engineering, Life Sciences

M. Schalk

Firmenich Inc.

L. Daviet

Firmenich Inc.

Jens B Nielsen

Chalmers, Chemical and Biological Engineering, Life Sciences

Microbial Cell Factories

14752859 (eISSN)

Vol. 11 Article Number: 117- 117

Driving Forces

Sustainable development

Subject Categories

Biological Sciences

Areas of Advance

Energy

Life Science Engineering (2010-2018)

DOI

10.1186/1475-2859-11-117

More information

Latest update

9/6/2018 1