The systematic method has been published in Nucleic acids research. We have to update the data which we collected from databases, such as KEGG, Uni-ProtKB. The MetaCyc database contains a lot of data which has been provided by experiment, so we have to try to integrate their data. Before that, based on KEGG map, we did not integrate MetaCyc data. Figure 6.1 shows the summary of my study (blue box). In the future, we may try to prove the problem by experiments, because we have obtained three key enzymes for synthesis resveratrol (see Table 6.1). Finally, the following step and result will implement the synthetic biology.
Figure 6.1 Summary and future work
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Table 6.1 The plasmid for resveratrol biosynthesis in E. coli
Gene name Vector Origin Anti Restriction E Gene Sequence Promoter
PAL pET16b based pBR322 Amp Nde1 : BamH1 X13094.1 T7
4CL pBluescript SK- pUC Amp EcoR1 : Xho1 D49366.1
ACC
(dtsR1,accBC)
pRSFDuet-1 ColeE1 Kan BamH1:HindIII/Nde1:Xho1 unpublished T7
PMT pACYCDuet-1 CDF Cam EcoR1 : HindIII Contain res site T7
STS GeneSynthesis
Symbols: PAL: Phenylalanine ammonia lyase; 4CL: Cinnamate 4-hydroxylase; ACC: Acetyl-CoA carboxylase; PMT: Pinosylvin methyltransferase ; STS: Stilbene synthase
Reference
1. Dewick, P.M., Medicinal natural products: a biosynthetic approach. 2nd ed.
2002, Chichester: John Wiley & Sons, Ltd.
2. Channon, K., E.H. Bromley, and D.N. Woolfson, Synthetic biology through biomolecular design and engineering. Curr Opin Struct Biol, 2008. 18(4): p.
491-8.
3. Crozier, A., M.N. Clifford, and H. Ashihara, Plant Secondary Metabolites. 1st ed.
2006, Oxford: Blackwell Publishing Ltd.
4. Vermeris, W. and R. Nicholson, Phenolic Compound Biochemistry. 2006, Dordrecht: Springer.
5. Zhu, Y.Z., et al., Antioxidants in Chinese herbal medicines: a biochemical perspective. Nat Prod Rep, 2004. 21(4): p. 478-89.
6. Endy, D., Foundations for engineering biology. Nature, 2005. 438(7067): p.
449-53.
7. Heinemann, M. and S. Panke, Synthetic biology--putting engineering into biology. Bioinformatics, 2006. 22(22): p. 2790-9.
8. Prather, K.L. and C.H. Martin, De novo biosynthetic pathways: rational design of microbial chemical factories. Curr Opin Biotechnol, 2008. 19(5): p.
468-74.
9. Park, J.H. and S.Y. Lee, Towards systems metabolic engineering of
microorganisms for amino acid production. Curr Opin Biotechnol, 2008. 19(5):
p. 454-60.
10. Lee, J.H., et al., Global analyses of transcriptomes and proteomes of a parent strain and an L-threonine-overproducing mutant strain. J Bacteriol, 2003.
185(18): p. 5442-51.
11. Ohnishi, J., et al., A novel gnd mutation leading to increased L-lysine production in Corynebacterium glutamicum. FEMS Microbiol Lett, 2005.
242(2): p. 265-74.
12. Park, J.H., et al., Metabolic engineering of Escherichia coli for the production of L-valine based on transcriptome analysis and in silico gene knockout simulation. Proc Natl Acad Sci U S A, 2007. 104(19): p. 7797-802.
13. Ruckert, C., A. Puhler, and J. Kalinowski, Genome-wide analysis of the L-methionine biosynthetic pathway in Corynebacterium glutamicum by targeted gene deletion and homologous complementation. J Biotechnol, 2003.
104(1-3): p. 213-28.
14. Garg, R.P., et al., Investigations of valanimycin biosynthesis: elucidation of the
55
role of seryl-tRNA. Proc Natl Acad Sci U S A, 2008. 105(18): p. 6543-7.
15. Atsumi, S., T. Hanai, and J.C. Liao, Non-fermentative pathways for synthesis of branched-chain higher alcohols as biofuels. Nature, 2008. 451(7174): p.
86-9.
16. Diella, F., et al., Phospho.ELM: a database of experimentally verified
phosphorylation sites in eukaryotic proteins. BMC Bioinformatics, 2004. 5: p.
79.
17. Jensen, O.N., Interpreting the protein language using proteomics. Nat Rev Mol Cell Biol, 2006. 7(6): p. 391-403.
18. Kanehisa, M., et al., KEGG for linking genomes to life and the environment.
Nucleic Acids Res, 2008. 36(Database issue): p. D480-4.
19. Caspi, R., et al., The MetaCyc Database of metabolic pathways and enzymes and the BioCyc collection of Pathway/Genome Databases. Nucleic Acids Res, 2008. 36(Database issue): p. D623-31.
20. Chang, A., et al., BRENDA, AMENDA and FRENDA the enzyme information system: new content and tools in 2009. Nucleic Acids Res, 2009. 37(Database issue): p. D588-92.
21. Li, Y., et al., Metabolic pathway alignment between species using a
comprehensive and flexible similarity measure. BMC Syst Biol, 2008. 2: p.
111.
22. Boutet, E., et al., UniProtKB/Swiss-Prot. Methods Mol Biol, 2007. 406: p.
89-112.
23. Lee, T.Y., et al., A comprehensive resource for integrating and displaying protein post-translational modifications. BMC Res Notes, 2009. 2: p. 111.
24. Oehm, S., et al., Comparative Pathway Analyzer--a web server for
comparative analysis, clustering and visualization of metabolic networks in multiple organisms. Nucleic Acids Res, 2008. 36(Web Server issue): p.
W433-7.
25. Pommerenke, C., et al., ROSY--a flexible and universal database and bioinformatics tool platform for Roseobacter related species. In Silico Biol, 2008. 8(2): p. 177-86.
26. Katsuyama, Y., N. Funa, and S. Horinouchi, Precursor-directed biosynthesis of stilbene methyl ethers in Escherichia coli. Biotechnol J, 2007. 2(10): p.
1286-93.
27. Price, N.D., J.L. Reed, and B.O. Palsson, Genome-scale models of microbial cells: evaluating the consequences of constraints. Nat Rev Microbiol, 2004.
2(11): p. 886-97.
28. Reed, J.L., et al., An expanded genome-scale model of Escherichia coli K-12
(iJR904 GSM/GPR). Genome Biol, 2003. 4(9): p. R54.
29. Lee, T.Y., et al., dbPTM: an information repository of protein
post-translational modification. Nucleic Acids Res, 2006. 34(Database issue):
p. D622-7.
30. Carlson, R. and F. Srienc, Fundamental Escherichia coli biochemical pathways for biomass and energy production: identification of reactions.
Biotechnol Bioeng, 2004. 85(1): p. 1-19.
31. Schuster, S., D.A. Fell, and T. Dandekar, A general definition of metabolic pathways useful for systematic organization and analysis of complex metabolic networks. Nat Biotechnol, 2000. 18(3): p. 326-32.
32. Trinh, C.T., A. Wlaschin, and F. Srienc, Elementary mode analysis: a useful metabolic pathway analysis tool for characterizing cellular metabolism. Appl Microbiol Biotechnol, 2009. 81(5): p. 813-26.
33. von Kamp, A. and S. Schuster, Metatool 5.0: fast and flexible elementary modes analysis. Bioinformatics, 2006. 22(15): p. 1930-1.
34. Chou, C.H., et al., FMM: a web server for metabolic pathway reconstruction and comparative analysis. Nucleic Acids Res, 2009.
35. Ferrer, J.L., et al., Structure and function of enzymes involved in the biosynthesis of phenylpropanoids. Plant Physiol Biochem, 2008. 46(3): p.
356-70.
36. Kundu, J.K. and Y.J. Surh, Molecular basis of chemoprevention by resveratrol:
NF-kappaB and AP-1 as potential targets. Mutat Res, 2004. 555(1-2): p.
65-80.
37. Valenzano, D.R., et al., Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate. Curr Biol, 2006. 16(3): p.
296-300.
38. Beekwilder, J., et al., Production of resveratrol in recombinant microorganisms. Appl Environ Microbiol, 2006. 72(8): p. 5670-2.
39. Trinh, C.T., et al., Design, construction and performance of the most efficient biomass producing E. coli bacterium. Metab Eng, 2006. 8(6): p. 628-38.
40. Yazdani, S.S. and R. Gonzalez, Anaerobic fermentation of glycerol: a path to economic viability for the biofuels industry. Curr Opin Biotechnol, 2007. 18(3):
p. 213-9.
41. Martinez, K., et al., Coutilization of glucose and glycerol enhances the production of aromatic compounds in an Escherichia coli strain lacking the phosphoenolpyruvate: carbohydrate phosphotransferase system. Microb Cell Fact, 2008. 7: p. 1.
42. Baez-Viveros, J.L., et al., Metabolic engineering and protein directed
57
evolution increase the yield of L-phenylalanine synthesized from glucose in Escherichia coli. Biotechnol Bioeng, 2004. 87(4): p. 516-24.
43. Lutke-Eversloh, T. and G. Stephanopoulos, L-tyrosine production by deregulated strains of Escherichia coli. Appl Microbiol Biotechnol, 2007.
75(1): p. 103-10.
44. Olson, M.M., et al., Production of tyrosine from sucrose or glucose achieved by rapid genetic changes to phenylalanine-producing Escherichia coli strains.
Appl Microbiol Biotechnol, 2007. 74(5): p. 1031-40.