Abstract
Hydroxycinnamates are a class of phenolic compounds that have a C6-C3 carbon backbone. Hydroxycinnamic acids are derived from cinnamic acid via hydroxylation or methylation and are found in foods such as pears, coffee beans, and dandelions. They are involved in protection against chemotherapy side effects and the prevention of cardiovascular disease and cancer. We synthesized four types of hydroxycinnamates (p-coumaric acid, cinnamic acid, caffeic acid, and ferulic acid) from glucose in Escherichia coli by introducing different combination of four genes: tyrosine ammonia lyase, phenylalanine ammonia lyase, S.espanaensis monooxygenase, and Oryza sativa O-methyltransferase. The final yields of hydroxycinnamic acids were increased by engineering the metabolic pathway of E. coli. Using these strategies, 100.1 mg/L p-coumaric acid, 138.2 mg/L caffeic acid, 64 mg/L ferulic acid, and 1072.3 mg/L cinnamic acid were synthesized.
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Berner M, Krug D, Bihlmaier C, Vente A, Müller R, Bechthold A (2006) Genes and enzymes involved in caffeic acid biosynthesis in the actinomycete Saccharothrix espanaensis. J Bacteriol 188:2666–2673
Dixon RA, Paiva NL (1995) Stree-induced phenylpropanoid metabolism. Plant Cell 7:1085–1097
Forkmann G, Martens S (2001) Metabolic engineering and applications of flavonoids. Curr Opin Biotechnol 12:155–160
Furuya T, Arai Y, Kino K (2012) Biotechnological production of caffeic acid by bacterial cytochrome P450 CYP199A2. Appl Environ Microbiol 78:6087–6094
Huang M-T, Smart RC, Wong C-Q, Conney AH (1988) Inhibitory effect of curcumin, chlorogenic acid, caffeic acid, and ferulic acid on tumor promotion in mouse skin by 12-O-tetradecanoylphorbol-13-acetate. Cancer Res 48:5941–5946
Juminaga D, Baidoo EE, Redding-Johanson AM, Batth TS, Burd H, Mukhopadhyay A, Petzold CJ, Keasling JD (2012) Modular engineering of l-tyrosine production in Escherichia coli. Appl Environ Microbiol 78:89–98
Jung UJ, Lee MK, Park YB, Jeon SM, Choi MS (2006) Antihyperglycemic and antioxidant properties of caffeic acid in db/db mice. J Pharmacol Exp Ther 318:476–483
Kaneko T, Thi TH, Shi DJ, Akashi M (2006) Environmentally degradable, high-performance thermoplastics from phenolic phytomonomers. Nat Mater 2(5):966–970
Kang S-Y, Choi O, Lee JK, Hwang BY, Um T-B, Hong Y-S (2012) Artificial biosynthesis of phenylpropanoic acids in a tyrosine overproducing Escherichia coli strain. Microb Cell Fact 11:152
Kim BG, Lee Y, Hur H-G, Lim Y, Ahn J-H (2006) Flavonoid 3′-O-methyltransferase from rice: cDNA cloning, characterization and functional expression. Phytochemistry 67:387–394
Kim MJ, Kim B-G, Ahn J-H (2013) Biosynthesis of bioactive O-methylated flavonoids in Escherichia coli. Appl Microbiol Biotechnol 97:7195–7204
Lee H, Kim B-G, Ahn J-H (2014) Production of bioactive hydroxyflavones by using monooxygenase from Saccharothrix espanaensis. J Biotechnol 176:11–17
Luceri C, Giannini L, Lodovici M, Antonucci E, Abbate R, Masini E, Dolara P (2007) p-Coumaric acid, a common dietary phenol, inhibits platelet activity in vitro and in vivo. Br J Nutr 97:458–463
Lütke-Eversloh T, Stephanopoulos G (2007) L-Tyrosine production by deregulated strains of Escherichia coli. Appl Microbiol Biotechnol 75:103–110
Rodriguez A, Martinez JA, Flores N, Escalante A, Gosset G, Bolivar F (2014) Engineering Escherichia coli to overproduce aromatic amino acids and derived compounds. Microb Cell Fact 13:216
Rosler J, Krekel F, Amrhein N, Schmid J (1997) Maize phenylalanine ammonia-lyase has tyrosine ammonia- lyase activity. Plant Physiol 113:175–179
Sariaslani FS (2007) Development of a combined biological and chemical process for production of industrial aromatics from renewable resources. Annu Rev Microbiol 61:51–69
Tolia NH, Joshua-Tor L (2006) Strategies for protein coexpression in Escherichia coli. Nat Methods 3:55–64
Vargas-Tah A, Matinez LM, Hernádez-Chávez G, Rocha A, Martínez Bolívar F, Gosset G (2015) Production of cinnamic and p-hydroxycinnamic acid from sugar mixtures with engineered Escherichia coli. Microb Cell Fact 14:6
Vogt T (2010) Phenylpropanoid biosynthesis. Mol Plant 3:2–20
Wang S, Zhang S, Xiao A, Rasmussen M, Skidmore C, Zhan J (2015) Metabolic engineering of Escherichia coli for the biosynthesis of various phenylpropanoid derivatives. Metab Eng 29:153–159
Yang S-M, Shim GY, Kim B-G, Ahn J-H (2015) Biological synthesis of coumarins in Escherichia coli. Microb Cell Fact 14:65
Zhang H, Stephanopoulos G (2013) Engineering E. coli for caffeic acid biosynthesis from renewable sugars. Appl Microbiol Biotechnol 97:3333–3341
Acknowledgments
This work was supported by a grant from the Next-Generation BioGreen 21 Program (PJ00948301), the Rural Development Administration, and Priority Research Centers Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (2009-0093824).
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Dae Gyuun An and Mi Na Cha have contributed equally to this article.
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An, D.G., Cha, M.N., Nadarajan, S.P. et al. Bacterial synthesis of four hydroxycinnamic acids. Appl Biol Chem 59, 173–179 (2016). https://doi.org/10.1007/s13765-015-0137-4
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DOI: https://doi.org/10.1007/s13765-015-0137-4