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中国生物工程杂志

China Biotechnology
China Biotechnology
China Biotechnology  2020, Vol. 40 Issue (7): 91-99    DOI: 10.13523/j.cb.2002025
    
Advances in Production of Caffeic Acid and Its Ester Derivatives in Heterologous Microbes
WANG Zhen,LI Xia(),YUAN Ying-jin
Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering, Ministry of Education, Tianjin University, Tianjin 300072, China
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Abstract  

Caffeic acid and its ester derivatives like chlorogenic acid, rosmarinic acid, and caffeic acid phenethyl ester have important pharmacological activities such as natural antioxidant, antitumor, antiviral, and anti-inflammatory, and have broad prospects for medical development. Traditional extraction and chemical synthesis of caffeic acid and its derivatives from plants exist some problems such as low content, low extraction efficiency, high catalytic cost, and environmental pollution. In recent years, the study of heterologous synthesis of caffeic acid and its ester derivatives by microbes has been gradually carried out with the rapid development of synthetic biology.The recent advances in the biosynthetic pathway elucidations of caffeic acid and its ester derivatives and metabolic engineering strategies in heterologous microbes were summarized, and the current status as well as future perspectives were discussed.

Key words： Caffeic acid      Caffeic acid ester derivatives      Synthetic biology     
Received: 18 February 2020      Published: 13 August 2020
ZTFLH:  Q815  
Corresponding Authors: Xia LI     E-mail: lixia01@tju.edu.cn
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Zhen WANG
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Cite this article:

WANG Zhen,LI Xia,YUAN Ying-jin. Advances in Production of Caffeic Acid and Its Ester Derivatives in Heterologous Microbes. China Biotechnology, 2020, 40(7): 91-99.

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https://manu60.magtech.com.cn/biotech/10.13523/j.cb.2002025     OR     https://manu60.magtech.com.cn/biotech/Y2020/V40/I7/91

Fig.1 Chemical structure of caffeic acid and its common ester derivatives
Fig.2 Heterogeneous biosynthesis pathway (a) Biosynthesis pathway of caffeic acid (b) Biosynthesis pathway of caffeic acid ester derivatives PAL:Phenylalanine ammonia lyase; TAL:Tyrosine ammonia lyase; C4H:Cinnamate 4-hydroxylase; C3H:Cinnamate3-hydroxylase;fevV, ammonialyase;4CL:4-coumarate-CoA ligase; 4HPA3H: 4-hydroxy phenylacetate 3- monooxygenase; D-LDH:D-lactate dehydrogenase;KDC:2-keto-acid decarboxylase;ADH:Alcohol dehydrogenase; HQT:Hydroxycinnamate-CoA quinate transferase; RAS: Rosmarinic acid synthase;ATF:Acyltransferase
Product Precursor Carbon source Heterologous
enzymes		 Source Titer Host Ref.
Caffeic acid p-coumaric acid Glycerol CYP199A2
pdR
pux		 R. palustris
P. putida
R. palustris		 2.8g/L E.coli [17]
p-coumaric acid Glycerol hpaBC P.aeruginosa PAO1 10.2g/L E.coli [19]
Tyrosine Glucose TAL
hpaB
hpaC		 R. toruloides
P. aeruginosa
S. enterica		 289mg/L S. cerevisiae [20]
No added Glucose+
Glycerol		 TAL
hpaBC		 R. capsulatus
E. coli MG1655		 50.2mg/L E.coli [5]
No added Cellulose from
Kraft pulp		 fevV
hpaBC		 Streptomyces sp.
WK-5344
P.aeruginosa PAO1		 233mg/L E.coli [16]
Rosmarinic acid No added Glucose HdhA
hpaBC
TAL
4CL
RAS		 L. delbrueckii
E. coli
R. sphaeroides
A. thaliana
M. officinalis		 1.8μmol/L E.coli [7]
Caffeic acid Glucose LDH
hpaBC
4CL
RAS		 L. pentosus
E. coli
A.thaliana
Coleus blumei		 130mg/L E.coli [8]
Chlorogenic acid Caffeic acid Glucose 4CL
HQT
ydiB		 O. sativa
N. tobacco
E. coli		 450mg/L E.coli [10]
No added Glucose TAL
hpaBC
4CL
HQT
ydiB		 S.espanaensis
E. coli
O. sativa
N. tobacco
E. coli		 78mg/L E.coli [11]
Caffeic acid
phenethyl esters		 No added Glucose TAL
hpaBC
4CL
KDC
ADH
O-ATF		 R. glutinis
E. coli
A. thaliana
Lactococcus lactis
S. cerevisiae
S. cerevisiae		 60mg/L E.coli [13]
Table 1 Hterogeneous synthesis of caffeic acid and its ester derivatives in microbe hosts
Fig.3 Metabolic regulation of shikimate pathway in microbes G6P:Glucose-6-phosphate;F6P:Fructose-6-phosphate;Ru5P:Ribulose5-phosphate;R5P:Ribose-5-phosphate;X5P:Xylulose-5-phosphate;S7P:Sedoheptulose7-phosphate;PEP:Phosphoenolpyruvate;E4P:Erythrose-4-phosphate; Pyr:Pyruvate; Ac-CoA:Acetyl-CoA; DAHP: 3-deoxy-D-arabino-2-heptulosonic acid 7-phosphate; SHK:Shikimic acid; CHA:Chorismic acid; PP,:Phenylpyruvate; HPP:4-hydroxyphenylpyruvate; Tyr:Tyrosine; Phe:Phenylalanine
[1]   Espíndola K M M, Ferreira R G, Lem N, et al. Chemical and pharmacological aspects of caffeic acid and its activity in hepatocarcinoma. Frontiers in Oncology, 2019,9:541.
doi: 10.3389/fonc.2019.00541 pmid: 31293975
[2]   Cunha F M D, Duma D, Assreuy J, et al. Caffeic acid derivatives: in vitro and in vivo anti-inflammatory properties. Free Radical Research, 2004,38(11):1241-1253.
doi: 10.1080/10715760400016139 pmid: 15621702
[3]   Magnani C, Isaac V L B, Correa M A, et al. Caffeic acid: a review of its potential use in medications and cosmetics. Analytical Methods, 2014,6(10):3203-3210.
doi: 10.1039/c3ay41807c
[4]   Zhang P, Tang Y, Li N G, et al. Bioactivity and chemical synthesis of caffeic acid phenethyl ester and its derivatives. Molecules, 2014,19(10):16458-16476.
doi: 10.3390/molecules191016458 pmid: 25314606
[5]   Davy A M, Kildegaard H F, Anderson M R, et al. Cell factory engineering. Cell System, 2017,4(3):262-257.
doi: 10.1016/j.cels.2017.02.010
[6]   Zhang X, Liu C J. Multifaceted regulations of gateway enzyme phenylalanine ammonia-lyase in the biosynthesis of phenylpropanoids. Molecular Plant, 2015,8(1):17-27.
doi: 10.1016/j.molp.2014.11.001 pmid: 25578269
[7]   Kim Y H, Kwon T W, Yang H J, et al. Gene engineering, purification, crystallization and preliminary x-ray diffraction of cytochrome P450 p-coumarate-3-hydroxylase (C3H), the Arabidopsis membrane protein. Protein Expression and Purification, 2011,79(1):149-155.
doi: 10.1016/j.pep.2011.04.013
[8]   Berner M, Krug D, Bihlmaier C, et al. Genes and enzymes involved in caffeic acid biosynthesis in the Actinomycete Saccharothrix espanaensis. Journal of Bacteriology, 2006,188(7):2666-2673.
doi: 10.1128/JB.188.7.2666-2673.2006 pmid: 16547054
[9]   Lin Y, Yan Y. Biosynthesis of caffeic acid in Escherichia coli using its endogenous hydroxylase complex. Microbial Cell Factories, 2012,11(1):42.
doi: 10.1186/1475-2859-11-42
[10]   Maurya D K, Devasagayam T P A. Antioxidant and prooxidant nature of hydroxycinnamic acid derivatives ferulic and caffeic acids. Food and Chemical Toxicology, 2010,48(12):3369-3373.
doi: 10.1016/j.fct.2010.09.006 pmid: 20837085
[11]   Kim G D, Park Y S, Jin Y H, et al. Production and applications of rosmarinic acid and structurally related compounds. Applied Microbiology and Biotechnology, 2015,99(5):2083-2092.
doi: 10.1007/s00253-015-6395-6 pmid: 25620368
[12]   Petersen M. Rosmarinic acid: new aspects. Phytochemistry Reviews, 2013,12(1):207-227.
doi: 10.1007/s11101-013-9282-8
[13]   Bloch S E, Schmidt-Dannert C. Construction of a chimeric biosynthetic pathway for the De Novo biosynthesis of rosmarinic acid in Escherichia coli. Biochemistry, 2014,15(16):2393-2401.
[14]   Zhuang Y, Jiang J, Bi H, et al. Synthesis of rosmarinic acid analogues in Escherichia coli. Biotechnology Letters, 2016,38(4):619-627.
doi: 10.1007/s10529-015-2011-1 pmid: 26667131
[15]   Naveed M, Hejazi V, Abbas M, et al. Chlorogenic acid (CGA): A pharmacological review and call for further research. Biomedicine and Pharmacotherapy, 2018,97:67-74.
doi: 10.1016/j.biopha.2017.10.064 pmid: 29080460
[16]   Kim B G, Jung W D, Mok H, et al. Production of hydroxycinnamoyl-shikimates and chlorogenic acid in Escherichia coli: Production of hydroxycinnamic acid conjugates. Microbial Cell Factories, 2013,12(1):15.
doi: 10.1186/1475-2859-12-15
[17]   Armutcu F, Akyol S, Ustunsoy S, et al. Therapeutic potential of caffeic acid phenethyl ester and its anti-inflammatory and immunomodulatory effects (review). Experimental and Therapeutic Medicine, 2015,9(5):1582-1588
doi: 10.3892/etm.2015.2346 pmid: 26136862
[18]   Wang J, Mahajani M, Jackson S L, et al. Engineering a bacterial platform for total biosynthesis of caffeic acid derived phenethyl esters and amides. Metabolic Engineering, 2017,44:89-99.
doi: 10.1016/j.ymben.2017.09.011 pmid: 28943460
[19]   Wang Y, Chen S, Yu O. Metabolic engineering of flavonoids in plants and microorganisms. Applied Microbiology and Biotechnology, 2011,91(4):949-956.
doi: 10.1007/s00253-011-3449-2 pmid: 21732240
[20]   Cheon S, Kim H M, Gustavsson M, et al. Recent trends in metabolic engineering of microorganisms for the production of advanced biofuels. Current Opinion in Chemical Biology, 2016,35:10-21.
doi: 10.1016/j.cbpa.2016.08.003 pmid: 27552559
[21]   Zhang Y, Hess H. Toward rational design of high-efficiency enzyme cascade. ACS Catalysis, 2017,2017(7):6018-6027.
[22]   Jendresen C B, Stahlhut S G, Li M, et al. Highly active and specific tyrosine ammonia-lyases from diverse origins enable enhanced production of aromatic compounds in bacteria and Saccharomyces cerevisiae. Applied and Environmental Microbiology, 2015,81(13):4458-4476.
doi: 10.1128/AEM.00405-15 pmid: 25911487
[23]   Kawaguchi H, Katsuyama Y, Danyao D, et al. Caffeic acid production by simultaneous saccharification and fermentation of kraft pulp using recombinant Escherichia coli. Applied Microbiology and Biotechnology, 2017,101(13):5279-5290.
doi: 10.1007/s00253-017-8270-0 pmid: 28396925
[24]   Furuya T, Arai Y, Kino K. Biotechnological production of caffeic acid by bacterial cytochrome P450 CYP199A2. Applied and Environmental Microbiology, 2012,78(17):6087-6094.
doi: 10.1128/AEM.01103-12 pmid: 22729547
[25]   Galán B, Díaz E, Prieto M A, et al. Functional analysis of the small component of the 4-hydroxyphenylacetate 3-monooxygenase of Escherichia coli W: a prototype of a new Flavin:NAD(P)H reductase subfamily. Journal of Bacteriology, 2000,182(3):627-636.
doi: 10.1128/jb.182.3.627-636.2000 pmid: 10633095
[26]   Furuya T, Kino K. Catalytic activity of the two-component flavin-dependent monooxygenase from Pseudomonas aeruginosa toward cinnamic acid derivatives. Applied Microbiology and Biotechnology, 2014,98(3):1145-1154.
doi: 10.1007/s00253-013-4958-y
[27]   Liu L, Liu H, Zhang W, et al. Engineering the biosynthesis of caffeic acid in Saccharomyces cerevisiae with heterologous enzyme combinations. Engineering, 2019,5(2):287-295.
doi: 10.1016/j.eng.2018.11.029
[28]   Berger A, Petersen M M. Rosmarinic acid synthase is a new member of the superfamily of BAHD acyltransferases. Planta, 2006,224(6):1503-1510.
doi: 10.1007/s00425-006-0393-y
[29]   Eudes A, Mouille M, Robinson D S, et al. Exploiting members of the BAHD acyltransferase family to synthesize multiple hydroxycinnamate and benzoate conjugates in yeast. Microbial Cell Factories, 2016,15(1):198.
doi: 10.1186/s12934-016-0593-5 pmid: 27871334
[30]   Biggs B W, De Paepe B, Santos C N S, et al. Multivariate modular metabolic engineering for pathway and strain optimization. Current Opinion in Biotechnology, 2014,29:156-162.
doi: 10.1016/j.copbio.2014.05.005
[31]   Jossek R, Bongaerts J, Sprenger G A. Characterization of a new feedback-resistant 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase AroF of Escherichia coli. FEMS Microbiology Letters, 2001,202(1):145-148.
pmid: 11506923
[32]   姚元锋, 赵广荣. L-酪氨酸代谢工程研究进展. 食品与发酵工业, 2013,(5):136-141.
[32]   Yao Y F, Zhao G R. Advances on metabolic engineering of L-tyrosine. Food and Fermentation Industries, 2013,(5):136-141.
[33]   Kang S Y, Choi O, Lee J, et al. Artificial biosynthesis of phenylpropanoic acids in a tyrosine over-producing Escherichia coli strain. Microbial Cell Factories, 2012,11(1):153.
[34]   Rodrigues J L, Araújo R G, Prather K L J, et al. Heterologous production of caffeic acid from tyrosine in Escherichia coli. Enzyme and Microbial Technology, 2015,71:36-44.
doi: 10.1016/j.enzmictec.2015.01.001 pmid: 25765308
[35]   Huang J, Lin Y, Yuan Q, et al. Production of tyrosine through phenylalanine hydroxylation bypasses the intrinsic feedback inhibition in Escherichia coli. Journal of Industrial Microbiology & Biotechnology, 2015,42(4):655-659.
doi: 10.1007/s10295-015-1591-z pmid: 25645094
[36]   王钦, 曾伟主, 周景文. 大肠杆菌酪氨酸转运系统基因敲除对酪氨酸生产的影响. 生物工程学报, 2019,35(7):1247-1255.
doi: 10.13345/j.cjb.180533 pmid: 31328481
[36]   Wang Q, Zeng W Z, Zhou J W, et al. Effect of gene knockout of L-tyrosine transport system on L-tyrosine production in Escherichia coli. Chinese Journal of Biotechnology, 2019,35(7):1247-1255.
doi: 10.13345/j.cjb.180533 pmid: 31328481
[37]   Liu Q L, Yu T, Li X W, et al. Rewiring carbon metabolism in yeast for high level production of aromatic chemicals. Nature Communication, 2019,10(1):1-13.
[38]   Goers L, Freemont P, Polizzi K M. Co-culture systems and technologies: taking synthetic biology to the next level. Journal of The Royal Society Interface, 2014,11(96):65.
[39]   Zhang W, Liu H, Li X, et al. Production of naringenin from D-xylose with co-culture of E. coli and S. cerevisiae. Engineering in Life Sciences, 2017,17(9):1021-1029.
[40]   Li Z H, Wang X N, Zhang H R. Balancing the non-linear rosmarinic acid biosynthetic pathway by modular co-culture engineering, Metabolic Engineering, 2019,54:1-11.
doi: 10.1016/j.ymben.2019.03.002 pmid: 30844431
[41]   Cha M N, Kim H J, Kim B G, et al. Synthesis of chlorogenic acid and p-coumaroyl shikimates from glucose using engineered Escherichia coli. Journal of Microbiology and Biotechnology, 2014,24(8):1109-1117.
doi: 10.4014/jmb.1403.03033 pmid: 24786529
[42]   Ahn J O, Lee H W, Saha R, et al. Exploring the effects of carbon sources on metabolic capacity for shikimic acid production in Escherichia coli using in silico metabolic predictions. Journal of Microbiology and Biotechnology, 2008,18(11):1773-1784.
pmid: 19047820
[43]   Huang Q, Lin Y, Yan Y, et al. Caffeic acid production enhancement by engineering a phenylalanine over-producing. Biotechnology and Bioengineering, 2013,110(12):3188-3196.
doi: 10.1002/bit.24988 pmid: 23801069
[44]   Annaluru N, Muller H, Mitchell L A, et al. Total synthesis of a functional designer eukaryotic chromosome. Science, 2014,344(6179):55-58.
doi: 10.1126/science.1249252 pmid: 24674868
[45]   Richardson S M, Mitchell L A, Stracquadanio G, et al. Design of a synthetic yeast genome. Science, 2017,355(6329):1040-1044.
doi: 10.1126/science.aaf4557 pmid: 28280199
[46]   Xie Z X, Li B Z, Mitchell L A, et al. Perfect designer chromosome V and behavior of a ring derivative. Science, 2017, 355(6329): eaaf4704.
doi: 10.1126/science.abd3902 pmid: 32764055
[47]   Wu Y, Li B Z, Zhao M, et al. Bug mapping and fitness testing of chemically synthesized chromosome X. Science, 2017, 355(6329): eaaf4706.
doi: 10.1126/science.abd3902 pmid: 32764055
[48]   Shen M J, Wu Y, Yang K, et al. Heterozygous diploid and interspecies SCRaMbLEing. Nature Communications, 2018,9(1):1934.
doi: 10.1038/s41467-018-04157-0 pmid: 29789590
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