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Production of 3-geranyl-4-hydroxybenzoate acid in yeast, an important intermediate of shikonin biosynthesis pathway.

Authors
  • Wang, Sheng1
  • Wang, Ruishan1
  • Liu, Tan1
  • Zhan, Zhilai1
  • Kang, Liping1
  • Wang, Yanan1
  • Lv, Chaogeng1
  • Werck-Reichhart, Daniele2
  • Guo, Lanping1
  • Huang, Luqi1
  • 1 State Key Laboratory Breeding Base of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16 Nanxiaojienei, Dongzhimen, Dongcheng District, 100700 Beijing, China. , (China)
  • 2 Institute of Plant Molecular Biology, Centre National de la Recherche Scientifique (CNRS), University of Strasbourg, 12, rue du général Zimmer, F-67084 Strasbourg cedex, France. , (France)
Type
Published Article
Journal
FEMS Yeast Research
Publisher
Oxford University Press
Publication Date
Nov 01, 2017
Volume
17
Issue
7
Identifiers
DOI: 10.1093/femsyr/fox065
PMID: 28934417
Source
Medline
Keywords
License
Unknown

Abstract

Shikonin and its derivatives are the main active components in the medicinal plant Arnebia euchroma and possess extensive pharmaceutical properties. In this study, we developed an optimized yeast system to obtain high-level production of 3-geranyl-4-hydroxybenzoate acid (GBA), an important intermediate involved in shikonin biosynthesis pathway. For host selection, recombinant expression of p-hydroxybenzoate:geranyltransferase (PGT) derived from A. euchroma was performed in Saccharomyces cerevisiae WAT11U strain and high yield monoterpene strain. In shake flask culture with 1 mM p-hydroxybenzoate acid (PHBA), they could yield GBA at 0.1567 and 20.8624 mg L-1, respectively. Additionally, AePGT6 showed higher enzymatic activity than its homologs. Moreover, by combining improvement in the homologous mevalonate pathway with reconstruction in the heterologous shikimic pathway, a de novo GBA synthesis pathway was constructed in StHP6tHC with co-overexpressed SctHMG1, optimized EcUbiC and AePGT6. A high titer of 179.29 mg L-1 GBA was achieved in StHP6tHC under shake flask fermentation with 1 mM PHBA. These results suggest that yeast could be engineered systematically to enable an efficient monoterpene-quinone or naphthoquinone production.

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