TY - JOUR

T1 - Production of the Fragrance Geraniol in Peroxisomes of a Product-Tolerant Baker's Yeast

AU - Gerke, Jennifer

AU - Frauendorf, Holm

AU - Schneider, Dominik

AU - Wintergoller, Maxim

AU - Hofmeister, Thomas

AU - Poehlein, Anja

AU - Zebec, Ziga

AU - Takano, Eriko

AU - Scrutton, Nigel S.

AU - Braus, Gerhard H.

N1 - Funding information: The study was funded by the ERA-IB project “TERPENOSOME: Engineered compartments for monoterpenoid production using synthetic biology” (funding reference number 031A337A) and the Deutsche Forschungsgemeinschaft (DFG BR1502/19-1). ZZ, NS, and ET was funded by Biotechnology and Biological Sciences Research Council (BB/L027593/1) as part of the ERA-IB TERPENOSOME project. Funding for Open Access publication was supported by Göttingen University. We thank Verena Gro?e, Ute Neef, Verena Hofer-Preetz, and Mechthild B?meke for their technical assistance, Maria Vinaixia for the data evaluation of the initial GC-MS experiments, and Aroma Chemical Services International GmbH for providing geraniol as reference. We also thank Virginia W. Cornish for providing LW2591Y and Helge Bode and Blagovesta Popova for providing plasmids. Funding. The study was funded by the ERA-IB project ?TERPENOSOME: Engineered compartments for monoterpenoid production using synthetic biology? (funding reference number 031A337A) and the Deutsche Forschungsgemeinschaft (DFG BR1502/19-1). ZZ, NS, and ET was funded by Biotechnology and Biological Sciences Research Council (BB/L027593/1) as part of the ERA-IB TERPENOSOME project. Funding for Open Access publication was supported by G?ttingen University.

PY - 2020/9/23

Y1 - 2020/9/23

N2 - Monoterpenoids, such as the plant metabolite geraniol, are of high industrial relevance since they are important fragrance materials for perfumes, cosmetics, and household products. Chemical synthesis or extraction from plant material for industry purposes are complex, environmentally harmful or expensive and depend on seasonal variations. Heterologous microbial production offers a cost-efficient and sustainable alternative but suffers from low metabolic flux of the precursors and toxicity of the monoterpenoid to the cells. In this study, we evaluated two approaches to counteract both issues by compartmentalizing the biosynthetic enzymes for geraniol to the peroxisomes of Saccharomyces cerevisiae as production sites and by improving the geraniol tolerance of the yeast cells. The combination of both approaches led to an 80% increase in the geraniol titers. In the future, the inclusion of product tolerance and peroxisomal compartmentalization into the general chassis engineering toolbox for monoterpenoids or other host-damaging, industrially relevant metabolites may lead to an efficient, low-cost, and eco-friendly microbial production for industrial purposes.

AB - Monoterpenoids, such as the plant metabolite geraniol, are of high industrial relevance since they are important fragrance materials for perfumes, cosmetics, and household products. Chemical synthesis or extraction from plant material for industry purposes are complex, environmentally harmful or expensive and depend on seasonal variations. Heterologous microbial production offers a cost-efficient and sustainable alternative but suffers from low metabolic flux of the precursors and toxicity of the monoterpenoid to the cells. In this study, we evaluated two approaches to counteract both issues by compartmentalizing the biosynthetic enzymes for geraniol to the peroxisomes of Saccharomyces cerevisiae as production sites and by improving the geraniol tolerance of the yeast cells. The combination of both approaches led to an 80% increase in the geraniol titers. In the future, the inclusion of product tolerance and peroxisomal compartmentalization into the general chassis engineering toolbox for monoterpenoids or other host-damaging, industrially relevant metabolites may lead to an efficient, low-cost, and eco-friendly microbial production for industrial purposes.

KW - geraniol

KW - peroxisomes

KW - Saccharomyces cerevisiae

KW - compartmentalization

KW - tolerance

KW - monoterpenoids

UR - http://www.scopus.com/inward/record.url?scp=85092132727&partnerID=8YFLogxK

U2 - 10.3389/fbioe.2020.582052

DO - 10.3389/fbioe.2020.582052

M3 - Article

VL - 8

JO - Frontiers in Bioengineering and Biotechnology

JF - Frontiers in Bioengineering and Biotechnology

SN - 2296-4185

M1 - 582052

ER -