Modulating the Precursor and Terpene Synthase Supply for the Whole-Cell Biocatalytic Production of the Sesquiterpene (+)-Zizaene in a Pathway Engineered E. coli

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dc.identifier.uri http://dx.doi.org/10.15488/5097
dc.identifier.uri https://www.repo.uni-hannover.de/handle/123456789/5141
dc.contributor.author Aguilar, Francisco ger
dc.contributor.author Scheper, Thomas ger
dc.contributor.author Beutel, Sascha ger
dc.date.accessioned 2019-07-03T10:36:00Z
dc.date.available 2019-07-03T10:36:00Z
dc.date.issued 2019
dc.identifier.citation Aguilar, F.; Scheper, T.; Beutel, S.: Modulating the Precursor and Terpene Synthase Supply for the Whole-Cell Biocatalytic Production of the Sesquiterpene (+)-Zizaene in a Pathway Engineered E. coli. In: Genes 10 (2019), Nr. 6, 478. DOI: https://doi.org/10.3390/genes10060478 ger
dc.description.abstract The vetiver essential oil from Chrysopogon zizanioides contains fragrant sesquiterpenes used widely in the formulation of nearly 20% of men’s cosmetics. The growing demand and issues in the supply have raised interest in the microbial production of the sesquiterpene khusimol, the main compound of the vetiver essential oil due to its woody smell. In this study, we engineered the biosynthetic pathway for the production of (+)-zizaene, the immediate precursor of khusimol. A systematic approach of metabolic engineering in Escherichia coli was applied to modulate the critical bottlenecks of the metabolic flux towards (+)-zizaene. Initially, production of (+)-zizaene was possible with the endogenous methylerythritol phosphate pathway and the codon-optimized zizaene synthase (ZS). Raising the precursor E,E-farnesyl diphosphate supply through the mevalonate pathway improved the (+)-zizaene titers 2.7-fold, although a limitation of the ZS supply was observed. To increase the ZS supply, distinct promoters were tested for the expression of the ZS gene, which augmented 7.2-fold in the (+)-zizaene titers. Final metabolic enhancement for the ZS supply by using a multi-plasmid strain harboring multiple copies of the ZS gene improved the (+)-zizaene titers 1.3-fold. The optimization of the fermentation conditions increased the (+)-zizaene titers 2.2-fold, achieving the highest (+)-zizaene titer of 25.09 mg L−1. This study provides an alternative strategy to enhance the terpene synthase supply for the engineering of isoprenoids. Moreover, it demonstrates the development of a novel microbial platform for the sustainable production of fragrant molecules for the cosmetic industry. ger
dc.description.sponsorship Ministry of Science, Technology and Telecommunications of Costa Rica (MICITT)/PINN program/PED-058-2015-1/EU ger
dc.language.iso eng ger
dc.publisher Basel : MDPI
dc.relation info:eu-repo/grantAgreement/Ministry of Science, Technology and Telecommunications of Costa Rica (MICITT)/PINN program/PED-058-2015-1/EU ger
dc.relation.ispartofseries Genes 10 (2019), Nr. 6 ger
dc.rights CC BY 4.0 ger
dc.rights.uri https://creativecommons.org/licenses/by/4.0/ ger
dc.subject khusimene eng
dc.subject (+)-zizaene eng
dc.subject vetiver essential oil eng
dc.subject khusimol eng
dc.subject sesquiterpenes eng
dc.subject microbial production eng
dc.subject metabolic engineering eng
dc.subject Khusimen ger
dc.subject (+)-Zizaen ger
dc.subject Vetiveröl ger
dc.subject Khusimol ger
dc.subject Sesquiterpene ger
dc.subject Mikrobielle Produktion ger
dc.subject.ddc 500 | Naturwissenschaften ger
dc.subject.ddc 570 | Biowissenschaften, Biologie ger
dc.title Modulating the Precursor and Terpene Synthase Supply for the Whole-Cell Biocatalytic Production of the Sesquiterpene (+)-Zizaene in a Pathway Engineered E. coli ger
dc.type article ger
dc.type Text ger
dc.relation.doi 10.3390/genes10060478
dc.description.version publishedVersion ger
tib.accessRights frei zug�nglich ger


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