RESEARCH ARTICLE

Profiling influences of gene overexpression on heterologous resveratrol production in Saccharomyces cerevisiae

  • Duo Liu 1,2 ,
  • Bingzhi Li 1,2 ,
  • Hong Liu 1,2 ,
  • Xuejiao Guo 1,2 ,
  • Yingjin Yuan , 1,2
Expand
  • 1. Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China
  • 2. SynBio Research Platform, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin University, Tianjin 300072, China

Received date: 25 Jun 2016

Accepted date: 10 Aug 2016

Published date: 17 Mar 2017

Copyright

2017 Higher Education Press and Springer-Verlag Berlin Heidelberg

Abstract

Metabolic engineering of heterologous resveratrol production in Saccharomyces cerevisiae faces challenges as the precursor L-tyrosine is stringently regulated by a complex biosynthetic system. We overexpressed the main gene targets in the upstream pathways to investigate their influences on the downstream resveratrol production. Single-gene overexpression and DNA assembly-directed multigene overexpression affect the production of resveratrol as well as its precursor p-coumaric acid. Finally, the collaboration of selected gene targets leads to an optimal resveratrol production of 66.14±3.74 mg·L–1, 2.27 times higher than the initial production in YPD medium (4% glucose). The newly discovered gene targets TRP1 expressing phosphoribosylanthranilate isomerase, ARO3 expressing 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase, and 4CL expressing 4-coumaryl-CoA ligase show notable positive impacts on resveratrol production in S. cerevisiae.

Cite this article

Duo Liu , Bingzhi Li , Hong Liu , Xuejiao Guo , Yingjin Yuan . Profiling influences of gene overexpression on heterologous resveratrol production in Saccharomyces cerevisiae[J]. Frontiers of Chemical Science and Engineering, 2017 , 11(1) : 117 -125 . DOI: 10.1007/s11705-016-1601-3

Acknowledgments

The authors declare no competing financial interest. This work was funded by the National Basic Research Program of China (973 Program, Grant No. 2014CB745100) and the National High Technology Research and Development Program of China (863 Program, Grant No. 2012AA02A701), the International S&T Cooperation Program of China (2015DFA00960), and the National Natural Science Foundation of China (Major Program, Grant No. 21390203).ƒ

Electronic Supplementary Material

Supplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s11705-016-1601-3 and is accessible for authorized users.
1
Jeandet P, Delaunois B, Aziz A, Donnez D, Vasserot Y, Cordelier S, Courot E. Metabolic engineering of yeast and plants for the production of the biologically active hydroxystilbene, resveratrol. Journal of Biomedicine & Biotechnology, 2012, 579089

2
Mei Y Z, Liu R X, Wang D P, Wang X, Dai C C. Biocatalysis and bio-transformation of resveratrol in microorganisms. Biotechnology Letters, 2015, 37(1): 9–18

DOI

3
Borodina I, Nielsen J. Advances in metabolic engineering of yeast Saccharomyces cerevisiae for production of chemicals. Biotechnology Journal, 2014, 9(5): 609–620

DOI

4
Becker J V, Armstrong G O, vander Merwe M J, Lambrechts M G, Vivier M A, Pretorius I S. Metabolic engineering of Saccharomyces cerevisiae for the synthesis of the wine-related antioxidant resveratrol. FEMS Yeast Research, 2003, 4(1): 79–85

DOI

5
Beekwilder J, Wolswinkel R, Jonker H, Hall R, deVos C H, Bovy A. Production of resveratrol in recombinant microorganisms. Applied and Environmental Microbiology, 2006, 72(8): 5670–5672

DOI

6
Zhang Y, Li S Z, Li J, Pan X, Cahoon R E, Jaworski J G, Wang X, Jez J M, Chen F, Yu O. Using unnatural protein fusions to engineer resveratrol biosynthesis in yeast and Mammalian cells. Journal of the American Chemical Society, 2006, 128(40): 13030–13031

DOI

7
Shin S Y, Jung S M, Kim M D, Han N S, Seo J H. Production of resveratrol from tyrosine in metabolically engineered Saccharomyces cerevisiae. Enzyme and Microbial Technology, 2012, 51(4): 211–216

DOI

8
Trantas E, Panopoulos N, Ververidis F. Metabolic engineering of the complete pathway leading to heterologous biosynthesis of various flavonoids and stilbenoids in Saccharomyces cerevisiae. Metabolic Engineering, 2009, 11(6): 355–366

DOI

9
Yan Y, Kohli A, Koffas M A. Biosynthesis of natural flavanones in Saccharomyces cerevisiae. Applied and Environmental Microbiology, 2005, 71(9): 5610–5613

DOI

10
Kumar S, Omer S, Chitransh S, Khan B M. Cinnamate 4-hydroxylase downregulation in transgenic tobacco alters transcript level of other phenylpropanoid pathway genes. International Journal of Advanced Biotechnology and Research, 2012, 3(2): 545–557

11
Wang Y, Halls C, Zhang J, Matsuno M, Zhang Y, Yu O. Stepwise increase of resveratrol biosynthesis in yeast Saccharomyces cerevisiae by metabolic engineering. Metabolic Engineering, 2011, 13(5): 455–463

DOI

12
Wang Y, Yu O. Synthetic scaffolds increased resveratrol biosynthesis in engineered yeast cells. Journal of Biotechnology, 2012, 157(1): 258–260

DOI

13
Luttik M A, Vuralhan Z, Suir E, Braus G H, Pronk J T, Daran J M. Alleviation of feedback inhibition in Saccharomyces cerevisiae aromatic amino acid biosynthesis: Quantification of metabolic impact. Metabolic Engineering, 2008, 10(3-4): 141–153

DOI

14
Rodriguez A, Kildegaard K R, Li M, Borodina I, Nielsen J. Establishment of a yeast platform strain for production of p-coumaric acid through metabolic engineering of aromatic amino acid biosynthesis. Metabolic Engineering, 2015, 31: 181–188

DOI

15
Koopman F, Beekwilder J, Crimi B, van Houwelingen A, Hall R D, Bosch D, van Maris A J, Pronk J T, Daran J M. De novo production of the flavonoid naringenin in engineered Saccharomyces cerevisiae. Microbial Cell Factories, 2012, 11(1): 155

DOI

16
Juminaga D, Baidoo E E K, Redding-Johanson A M, Batth T S, Burd H, Mukhopadhyay A, Petzold C J, Keasling J D. Modular engineering of L-tyrosine production in Escherichia coli. Applied and Environmental Microbiology, 2012, 78(1): 89–98

DOI

17
Reid R J, Sunjevaric I, Kedacche M, Rothstein R. Efficient PCR-based gene disruption in Saccharomyces strains using intergenic primers. Yeast (Chichester, England), 2002, 19(4): 319–328

DOI

18
Gietz R D, Schiestl R H, Willems A R, Woods R A. Studies on the transformation of intact yeast cells by the LiAc/SS-DNA/PEG procedure. Yeast (Chichester, England), 1995, 11(4): 355–360

DOI

19
Sun J, Shao Z Y, Zhao H, Nair N, Wen F, Xu J H, Zhao H. Cloning and characterization of a panel of constitutive promoters for applications in pathway engineering in Saccharomyces cerevisiae. Biotechnology and Bioengineering, 2012, 109(8): 2082–2092

DOI

20
Shao Z, Zhao H, Zhao H. DNA assembler, an in vivo genetic method for rapid construction of biochemical pathways. Nucleic Acids Research, 2008, 37(2): e16

DOI

21
Sydor T, Schaffer S, Boles E. Considerable increase in resveratrol production by recombinant industrial yeast strains with use of rich medium. Applied and Environmental Microbiology, 2010, 76(10): 3361–3363

DOI

22
Braus G, Paravicini G, Hütter R. A consensus transcription termination sequence in the promoter region is necessary for efficient gene expression of the TRP1 gene of Saccharomyces cerevisiae. Molecular & General Genetics, 1988, 212(3): 495–504

DOI

23
Kim S, Mellor J, Kingsman A J, Kingsman S M. Multiple control element in the TRP1 promoter of Saccharomyces cerevisiae. Molecular and Cellular Biology, 1986, 6(12): 4251–4258

DOI

24
Teshiba S, Furter R, Niederberger P, Braus G, Paravicini G. Cloning of the ARO3 gene of Saccharomyces cerevisiae and its regulation. Molecular & General Genetics, 1986, 205(2): 353–357

DOI

25
Du J, Yuan Y B, Si T, Lian J Z, Zhao H M. Customized optimization of metabolic pathways by combinatorial transcriptional engineering. Nucleic Acids Research, 2012, 40(18): e142

DOI

26
Luo Y, Li B Z, Liu D, Zhang L, Chen Y, Jia B, Zeng B X, Zhao H, Yuan Y J. Engineered biosynthesis of natural products in heterologous hosts. Chemical Society Reviews, 2015, 44(15): 5265–5290

DOI

27
Santos C N, Stephanopoulos G. Melanin-based high-throughput screen for L-tyrosine production in Escherichia coli. Applied and Environmental Microbiology, 2008, 74(4): 1190–1197

DOI

Outlines

/