Abstract
Trans-resveratrol (trans-3,5,4′-trihydroxystilbene) is one of the most promising stilbenes, a type of natural phenol that is produced naturally by some plant species in response to stress. Resveratrol exhibits multiple bioactivities and is used in the agriculture, medical, food, and cosmetic industries due to its antitumor, anti-inflammatory, cardioprotective, and antioxidant properties. Due to the increasing demand, an active area of investigation is the use of plant cell culture and metabolic engineering techniques to produce large quantities of active resveratrol. However, most recent studies have focused on the efficiency of synthesizing resveratrol in vitro, but have not investigated the contributions of the transcriptional activities of the genes encoding the related enzymes in the biosynthesis pathway. This article reviews recently developed methods for the biosynthesis of resveratrol and comprehensively reviews the current state of knowledge of the function of the key pathway enzymes in resveratrol synthesis. Approaches for enhancing resveratrol production, such as introducing non-pathway genes and co-localizing enzymes are described in detail.
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References
Achnine L, Blancaflor EB, Rasmussen S, Dixon RA (2004) Colocalization of L-phenylalanine ammonia-lyase and cinnamate 4-hydroxylase for metabolic channeling in phenylpropanoid biosynthesis. Plant Cell 16:3098–3109. doi:10.1105/tpc.104.024406
Aleynova OA, Dubrovina AS, Manyakhin AY, Karetin YA, Kiselev KV (2015) Regulation of resveratrol production in Vitis amurensis cell cultures by calcium-dependent protein kinases. Appl Biochem Biotechnol 175:1460–1476. doi:10.1007/s12010-014-1384-2
Aleynova-Shumakova OA, Dubrovina AS, Manyakhin AY, Karetin YA, Kiselev KV (2014) VaCPK20 gene overexpression significantly increased resveratrol content and expression of stilbene synthase genes in cell cultures of Vitis amurensis Rupr. Appl Microbiol Biotechnol 98:5541–5549. doi:10.1007/s00253-014-5625-7
Almagro L, Belchi-Navarro S, Martinez-Marquez A, Bru R, Pedreno MA (2015) Enhanced extracellular production of trans-resveratrol in Vitis vinifera suspension cultured cells by using cyclodextrins and coronatine. Plant Physiol Biochem 97:361–367. doi:10.1016/j.plaphy.2015.10.025
Anthony JR, Anthony LC, Nowroozi F, Kwon G, Newman JD, Keasling JD (2009) Optimization of the mevalonate-based isoprenoid biosynthetic pathway in Escherichia coli for production of the anti-malarial drug precursor amorpha-4,11-diene. Metab Eng 11:13–19. doi:10.1016/j.ymben.2008.07.007
Batard Y, Schalk M, Pierrel M, Zimmerlin A, Durst F, Werck-Reichhart D (1997) Regulation of the cinnamate 4-hydroxylase (CYP73Al) in Jerusalem artichoke tubers in response to wounding and chemical treatments. Plant Physiol 113:951–959. doi:10.1104/pp.113.3.951
Becker JVW, Armstrong GO, van der Merwe MJ, Lambrechts MG, Vivier MA, Pretorius IS (2003) Metabolic engineering of Saccharomyces cerevisiae for the synthesis of the wine-related antioxidant resveratrol. FEMS Yeast Res 4:79–85. doi:10.1016/s1567-1356(03)00157-0
Belchi-Navarro S, Almagro L, Lijavetzky D, Bru R, Pedreno MA (2012) Enhanced extracellular production of trans-resveratrol in Vitis vinifera suspension cultured cells by using cyclodextrins and methyljasmonate. Plant Cell Rep 31:81–89. doi:10.1007/s00299-011-1141-8
Cai ZZ, Kastell A, Knorr D, Smetanska I (2012a) Exudation: an expanding technique for continuous production and release of secondary metabolites from plant cell suspension and hairy root cultures. Plant Cell Rep 31:461–477. doi:10.1007/s00299-011-1165-0
Cai ZZ, Kastell A, Speiser C, Smetanska I (2013) Enhanced resveratrol production in Vitis vinifera cell suspension cultures by heavy metals without loss of cell viability. Appl Biochem Biotechnol 171:330–340. doi:10.1007/s12010-013-0354-4
Cai ZZ, Knorr D, Smetanska I (2012b) Enhanced anthocyanins and resveratrol production in Vitis vinifera cell suspension culture by indanoyl-isoleucine, N-linolenoyl-L-glutamine and insect saliva. Enzym Microb Technol 50:29–34. doi:10.1016/j.enzmictec.2011.09.001
Çetin ES, Baydar NG (2016) Elicitor applications to cell suspension culture for production of phenolic compounds in grapevine. Tarım Bilimleri Dergisi 22:42–53
Cetin ES, Babalik Z, Hallac-Turk F, Gokturk-Baydar N (2014) The effects of cadmium chloride on secondary metabolite production in Vitis vinifera cv. cell suspension cultures. Biol Res 47:47. doi:10.1186/0717-6287-47-47
Chang MC, Eachus RA, Trieu W, Ro DK, Keasling JD (2007) Engineering Escherichia coli for production of functionalized terpenoids using plant P450s. Nat Chem Biol 3:274–277. doi:10.1038/nchembio875
Chen M, Li D, Gao ZQ, Zhang CZ (2014b) Enzymatic transformation of polydatin to resveratrol by piceid-β-d-glucosidase from Aspergillus oryzae. Bioprocess Biosyst Eng 37:1411–1416. doi:10.1007/s00449-013-1113-1
Chen HC, Song J, Wang JP, Lin YC, Ducoste J, Shuford CM, Liu J, Li Q, Shi R, Nepomuceno A, Isik F, Muddiman DC, Williams C, Sederoff RR, Chiang VL (2014a) Systems biology of lignin biosynthesis in Populus trichocarpa: heteromeric 4-coumaric acid:coenzyme A ligase protein complex formation, regulation, and numerical modeling. Plant Cell 26:876–893. doi:10.1105/tpc.113.119685
Chong JL, Poutaraud A, Hugueney P (2009) Metabolism and roles of stilbenes in plants. Plant Sci 177:143–155. doi:10.1016/j.plantsci.2009.05.012
Chung IM, Park MR, Chun JC, Yun SJ (2003) Resveratrol accumulation and resveratrol synthase gene expression in response to abiotic stresses and hormones in peanut plants. Plant Sci 164:103–109. doi:10.1016/S0168-9452(02)00341-2
Counet C, Callemien D, Sonia C (2006) Chocolate and cocoa: new sources of trans-resveratrol and trans-piceid. Food Chem 98:649–657. doi:10.1016/j.foodchem.2005.06.030
Dabauza M, Velasco L, Pazos-Navarro M, Perez-Benito E, Hellin P, Flores P, Gomez-Garay A, Martinez MC, Lacasa A (2015) Enhanced resistance to Botrytis cinerea in genetically-modified Vitis vinifera L. plants over-expressing the grapevine stilbene synthase gene. Plant Cell Organ Cult 120:229–238. doi:10.1007/s11240-014-0598-x
D’cunha GB, Satyanarayan V, Nair PM (1994) Novel direct synthesis of L-phenylalanine methyl ester by using Rhodotorula glutinis phenylalanine ammonia lyase in an organic-aqueous biphasic system. Enzym Microb Technol 16:318–322. doi:10.1016/0141-0229(94)90173-2
Delaunois B, Cordelier S, Conreux A, Clement C, Jeandet P (2009) Molecular engineering of resveratrol in plants. Plant Biotechnol J 7:2–12. doi:10.1111/j.1467-7652.2008.00377.x
Donnez D, Jeandet P, Clement C, Courot E (2009) Bioproduction of resveratrol and stilbene derivatives by plant cells and microorganisms. Trends Biotechnol 27:706–713. doi:10.1016/j.tibtech.2009.09.005
Du J, Shao ZY, Zhao HM (2011) Engineering microbial factories for synthesis of value-added products. J Ind Microbiol Biot 38:873–890. doi:10.1007/s10295-011-0970-3
Duan D, Halter D, Baltenweck R, Tisch C, Troster V, Kortekamp A, Hugueney P, Nick P (2015) Genetic diversity of stilbene metabolism in Vitis sylvestris. J Exp Bot 66:3243–3257. doi:10.1093/jxb/erv137
Dubrovina AS, Kiselev KV (2011) Effect of long-term cultivation on resveratrol accumulation in a high-producing cell culture of Vitis amurensis. Acta Physiol Plant 34:1101–1106. doi:10.1007/s11738-011-0907-5
Dubrovina AS, Kiselev KV, Veselova MV, Isaeva GA, Fedoreyev SA, Zhuravlev YN (2009) Enhanced resveratrol accumulation in rolB transgenic cultures of Vitis amurensis correlates with unusual changes in CDPK gene expression. J Plant Physiol 166:1194–1206. doi:10.1016/j.jplph.2009.01.006
Dueber JE, Wu GC, Malmirchegini GR, Moon TS, Petzold CJ, Ullal AV, Prather KL, Keasling JD (2009) Synthetic protein scaffolds provide modular control over metabolic flux. Nat Biotechnol 27:753–759. doi:10.1038/nbt.1557
Engels B, Dahm P, Jennewein S (2008) Metabolic engineering of taxadiene biosynthesis in yeast as a first step towards Taxol (paclitaxel) production. Metab Eng 10:201–206. doi:10.1016/j.ymben.2008.03.001
Fan EG, Zhang K, Zhu MZ, Wang Q (2010) Obtaining resveratrol: from chemical synthesis to biotechnological production. Mini-Rev Org Chem 7:272–281. doi:10.2174/157019310792246454
Fang LC, Hou YL, Wang LJ, Xin HP, Wang N, Li SH (2014) Myb14, a direct activator of STS, is associated with resveratrol content variation in berry skin in two grape cultivars. Plant Cell Rep 33:1629–1640. doi:10.1007/s00299-014-1642-3
Ferrer JL, Austin MB, Stewart Jr C, Noel JP (2008) Structure and function of enzymes involved in the biosynthesis of phenylpropanoids. Plant Physiol Biochem 46:356–370. doi:10.1016/j.plaphy.2007.12.009
Flores-Sanchez IJ, Verpoorte R (2009) Plant polyketide synthases: a fascinating group of enzymes. Plant Physiol Biochem 47:167–174. doi:10.1016/j.plaphy.2008.11.005
Fornara V, Onelli E, Sparvoli F, Rossoni M, Aina R, Marino G, Citterio S (2008) Localization of stilbene synthase in Vitis vinifera L. during berry development. Protoplasma 233:83–93. doi:10.1007/s00709-008-0309-8
Gao S, HN Y, RX X, Cheng AX, Lou HX (2015) Cloning and functional characterization of a 4-coumarate CoA ligase from liverwort Plagiochasma appendiculatum. Phytochemistry 111:48–58. doi:10.1016/j.phytochem.2014.12.017
Giovinazzo G, Ingrosso I, Paradiso A, Gara LD, Santino A (2012) Resveratrol biosynthesis: plant metabolic engineering for nutritional improvement of food. Plant Foods Hum Nutr 67:191–199. doi:10.1007/s11130-012-0299-8
Gonzalez-Candelas L, Gil JV, Lamuela-Raventos RM, Ramon D (2000) The use of transgenic yeasts expressing a gene encoding a glycosyl-hydrolase as a tool to increase resveratrol content in wine. Int J Food Microbiol 59:179–183. doi:10.1016/S0168-1605(00)00354-8
Halls C, Yu O (2008) Potential for metabolic engineering of resveratrol biosynthesis. Trends Biotechnol 26:77–81. doi:10.1016/j.tibtech.2007.11.002
Hasan MM, Cha M, Bajpai VK, Baek KH (2012) Production of a major stilbene phytoalexin, resveratrol in peanut (Arachis hypogaea) and peanut products: a mini review. Rev Environ Sci Biotechnol 12:209–221. doi:10.1007/s11157-012-9294-7
He S, Shi Y, Zhang SY, Zhang ZY (2015) Extraction of resveratrol and emondin from Polygonum cuspidatum by supercritical CO2 with different solubilizers. Afr J Pharm Pharmacol 9:12–18. doi:10.5897/ajpp2013.3816
Höll J, Vannozzi A, Czemmel S, D’Onofrio C, Walker AR, Rausch T, Lucchin M, Boss PK, Dry IB, Bogs J (2013) The R2R3-MYB transcription factors MYB14 and MYB15 regulate stilbene biosynthesis in Vitis vinifera. Plant Cell 25:4135–4149. doi:10.1105/tpc.113.117127
Jeandet P, Clément C, Courot E (2014) Resveratrol production at large scale using plant cell suspensions. Eng Life Sci 14:622–632. doi:10.1002/elsc.201400022
Jeandet P, Delaunois B, Aziz A, Donnez D, Vasserot Y, Cordelier S, Courot E (2012) Metabolic engineering of yeast and plants for the production of the biologically active hydroxystilbene, resveratrol. J Biomed Biotechnol 2012:1–14. doi:10.1155/2012/579089
Jeffrey Hurst W, Glinski JA, Miller KB, Apgar J, Davey MH, Stuart DA (2008) Survey of the trans-resveratrol and trans-piceid content of cocoa-containing and chocolate products. J Agric Food Chem 56:8374–8378. doi:10.1021/jf801297w
Jendresen CB, Stahlhut SG, Li M, Gaspar P, Siedler S, Forster J, Maury J, Borodina I, Nielsen AT (2015) Novel highly active and specific tyrosine ammonia-lyases from diverse origins enable enhanced production of aromatic compounds in bacteria and yeast. Appl Environ Microbiol 81:4458–4476. doi:10.1128/AEM.00405-15
Jerkovic V, Bröhan M, Monnart E, Nguyen F, Nizet S, Collin S (2010) Stilbenic profile of cocoa liquors from different origins determined by RP-HPLC-APCI (+)-MS/MS. Detection of a new resveratrol hexoside. J Agric Food Chem 58:7067–7074. doi:10.1021/jf101114c
Kang LZ, Li Q, Lin JF, Guo LQ (2015) Biosynthesis of resveratrol in blastospore of the macrofungus tremella fuciformis. Mol Biotechnol 57:675–684. doi:10.1007/s12033-015-9858-1
Keskin N, Kunter B (2008) Production of trans-resveratrol in “cabernet sauvignon” (Vitis vinifera L.) callus culture in response to ultraviolet-C irradiation. Vitis 47:193–196
Kiselev KV (2011) Perspectives for production and application of resveratrol. Appl Microbiol Biotechnol 90:417–425. doi:10.1007/s00253-011-3184-8
Kiselev KV, Dubrovina AS, Veselova MV, Bulgakov VP, Fedoreyev SA, Zhuravlev YN (2007) The rolB gene-induced overproduction of resveratrol in Vitis amurensis transformed cells. J Biotechnol 128:681–692. doi:10.1016/j.jbiotec.2006.11.008
Kiselev KV, Shumakova OA, Manyakhin AY (2013a) Effects of the calmodulin antagonist W7 on resveratrol biosynthesis in Vitis amurensis Rupr. Plant Mol Biol Report 31:1569–1575. doi:10.1007/s11105-013-0620-1
Kiselev KV, Shumakova OA, Manyakhin AY, Mazeika AN (2012) Influence of calcium influx induced by the calcium ionophore, A23187on resveratrol content and the expression of CDPK and STS genes in the cell cultures of Vitis amurensis. Plant Growth Regul 68:371–381. doi:10.1007/s10725-012-9725-z
Kiselev KV, Tyunin AP, Karetin YA (2015) Salicylic acid induces alterations in the methylation pattern of the VaSTS1, VaSTS2, and VaSTS10 genes in Vitis amurensis Rupr. Cell cultures. Plant Cell Rep 34:311–320. doi:10.1007/s00299-014-1708-2
Kiselev KV, Tyunin AP, Zhuravlev YN (2013b) Involvement of DNA methylation in the regulation of STS10 gene expression in Vitis amurensis. Planta 237:933–941. doi:10.1007/s00425-012-1806-8
Klein-Marcuschamer D, Yadav VG, Ghaderi A, Stephanopoulos GN (2010) De Novo metabolic engineering and the promise of synthetic DNA. Adv Biochem Eng Biot 120:101–131. doi:10.1007/10_2009_52
Kong JQ (2015) Phenylalanine ammonia-lyase, a key component used for phenylpropanoids production by metabolic engineering. RSC Adv 5:62587–62603. doi:10.1039/c5ra08196c
Kong JQ, Lu D, Wang ZB (2014) Molecular cloning and yeast expression of cinnamate 4-hydroxylase from Ornithogalum saundersiae baker. Molecules 19:1608–1621. doi:10.3390/molecules19021608
Krivoruchko A, Nielsen J (2015) Production of natural products through metabolic engineering of Saccharomyces cerevisiae. Curr Opin Biotech 35:7–15. doi:10.1016/j.copbio.2014.12.004
Kumar A, Ellis BE (2001) The phenylalanine ammonia-lyase gene family in raspberry. Structure, expression, and evolution. Plant Physiol 127:230–239. doi:10.1104/pp.127.1.230
Lancon A, Kaminski J, Tili E, Michaille JJ, Latruffe N (2012) Control of microRNA expression as a new way for resveratrol to deliver its beneficial effects. J Agric Food Chem 60:8783–8789. doi:10.1021/jf301479v
Laura R, Franceschetti M, Ferri M, Tassoni A, Bagni N (2007) Resveratrol production in Vitis vinifera cell suspensions treated with several elicitors. Caryologia 60:169–171. doi:10.1080/00087114.2007.10589568
Lee D, Lloyd NDR, Pretorius IS, Borneman AR (2016) Heterologous production of raspberry ketone in the wine yeast Saccharomyces cerevisiae via pathway engineering and synthetic enzyme fusion. Microb Cell Factories 15:1–7. doi:10.1186/s12934-016-0446-2
Leifer A, Barberio DM (2016) Direct ingestion method for enhancing production and bioavailability of resveratrol and other phytoalexins in Vitis vinifera. Med Hypotheses 88:1–5. doi:10.1016/j.mehy.2015.12.008
Li B, Wang BQ, Li HY, Peng L, Ru M, Liang ZS, Yan XJ, Zhu YH (2016) Establishment of Salvia castanea Diels F. tomentosa Stib. Hairy root cultures and the promotion of tanshinone accumulation and gene expression with Ag+, methyl jasmonate, and yeast extract elicitation. Protoplasma 253:87–100. doi:10.1007/s00709-015-0790-9
Li MJ, Kildegaard KR, Chen Y, Rodriguez A, Borodina I, Nielsen J (2015a) De novo production of resveratrol from glucose or ethanol by engineered Saccharomyces cerevisiae. Metab Eng 32:1–11. doi:10.1016/j.ymben.2015.08.007
Li Z, Nair SK (2015b) Structural basis for specificity and flexibility in a plant 4-coumarate: CoA ligase. Structure 23:2032–2042. doi:10.1016/j.str.2015.08.012
Li ZB, Li CF, Li J, Zhang YS (2014) Molecular cloning and functional characterization of two divergent 4-coumarate: coenzyme A ligases from kudzu (Pueraria lobata). Biol Pharm Bull 37:113–122. doi:10.1248/bpb.b13-00633
Lim CG, Fowler ZL, Hueller T, Schaffer S, Koffas MAG (2011) High-yield resveratrol production in engineered Escherichia coli. Appl Environ Microbiol 77:3451–3460. doi:10.1128/AEM.02186-10
Lin YH, Jain R, Yan YJ (2014) Microbial production of antioxidant food ingredients via metabolic engineering. Curr Opin Biotechnol 26:71–78. doi:10.1016/j.copbio.2013.10.004
Liu JY, Osbourn A, Ma P (2015) MYB transcription factors as regulators of phenylpropanoid metabolism in plants. Mol Plant 8:689–708. doi:10.1016/j.molp.2015.03.012
Liu XL, Lin J, HF H, Zhou B, Zhu BQ (2016) De novo biosynthesis of resveratrol by site-specific integration of heterologous genes in Escherichia coli. FEMS Microbiol Lett. doi:10.1093/femsle/fnw061
Lou JF, LY F, Peng YL, Zhou LG (2013) Metabolites from Alternaria fungi and their bioactivities. Molecules 18:5891–5935. doi:10.3390/molecules18055891
Lu Q, Zhao Q, QW Y, Feng YQ (2015) Use of pollen solid-phase extraction for the determination of trans-resveratrol in peanut oils. J Agr Food Chem 63:4771–4776. doi:10.1021/jf505938w
Luo YZ, Li BZ, Liu D, Zhang L, Chen Y, Jia B, Zeng BX, Zhao HM, Yuan YJ (2015) Engineered biosynthesis of natural products in heterologous hosts. Chem Soc Rev 44:5265–5290. doi:10.1039/C5CS00025D
MacDonald MC, Arivalagan P, Barre DE, MacInnis JA, D’Cunha GB (2016) Rhodotorula glutinis Phenylalanine/tyrosine ammonia lyase enzyme catalyzed synthesis of the methyl ester of para-hydroxycinnamic acid and its potential antibacterial activity. Front Microbiol 7:1–11. doi:10.3389/fmicb.2016.00281
Martinez RB, Garcia MAP (2007) Method for the production of resveratrol in cell cultures. Google Patents, United States
Martinez-Marquez A, Morante-Carriel JA, Ramirez-Estrada K, Cusido RM, Palazon J, Bru-Martinez R (2016) Production of highly bioactive resveratrol analogues pterostilbene and piceatannol in metabolically engineered grapevine cell cultures. Plant Biotechnol J 10:1–13. doi:10.1111/pbi.12539
Mei YZ, Liu RX, Wang DP, Wang X, Dai CC (2015) Biocatalysis and biotransformation of resveratrol in microorganisms. Biotechnol Lett 37:9–18. doi:10.1007/s10529-014-1651-x
Nishiyama Y, Yun CS, Matsuda F, Sasaki T, Saito K, Tozawa Y (2010) Expression of bacterial tyrosine ammonia-lyase creates a novel p-coumaric acid pathway in the biosynthesis of phenylpropanoids in Arabidopsis. Planta 232:209–218. doi:10.1007/s00425-010-1166-1
Nopo-Olazabal C, Hubstenberger J, Nopo-Olazabal L, Medina-Bolivar F (2013) Antioxidant activity of selected stilbenoids and their bioproduction in hairy root cultures of muscadine grape (Vitis rotundifolia Michx.). J Agr Food Chem 61:11744–11758. doi:10.1021/jf400760k
Pimentel FA, Nitzke JA, Klipel CB, Jong EV (2010) Chocolate and red wine - a comparison between flavonoids content. Food Chem 120:109–112. doi:10.1016/j.foodchem.2009.09.078
Pinto GP, Ribeiro AJM, Ramos MJ, Fernandes PA, Toscano M, Russo N (2015) New insights in the catalytic mechanism of tyrosine ammonia-lyase given by QM/MM and QM cluster models. Arch Biochem Biophys 582:107–115. doi:10.1016/j.abb.2015.03.002
Qi WW, Vannelli T, Breinig S, Ben-Bassat A, Gatenby AA, Haynie SL, Sariaslani FS (2007) Functional expression of prokaryotic and eukaryotic genes in Escherichia coli for conversion of glucose to p-hydroxystyrene. Metab Eng 9:268–276. doi:10.1016/j.ymben.2007.01.002
Ragg H, Kuhn DN, Hahlbrock K (1981) Coordinated regulation of 4-coumarate: CoA ligase and phenylalanine ammonia-lyase mRNAs in cultured plant cells. J Biol Chem 256:10061–10065
Rao GD, Pan X, Xu F, Zhang YZ, Cao S, Jiang XN, Lu H (2014) Divergent and overlapping function of five 4-coumarate/coenzyme A ligases from Populus tomentosa. Plant Mol Biol Rep 33:841–854. doi:10.1007/s11105-014-0803-4
Ruhmann S, Pfeiffer J, Brunner P, Szankowski I, Fischer TC, Forkmann G, Treutter D (2013) Induction of stilbene phytoalexins in grapevine (Vitis vinifera) and transgenic stilbene synthase-apple plants (Malus domestica) by a culture filtrate of Aureobasidium pullulans. Plant Physiol Biochem 72:62–71. doi:10.1016/j.plaphy.2013.03.011
Sales JM, Resurreccion AV (2014) Resveratrol in peanuts. Crit Rev Food Sci Nutr 54:734–770. doi:10.1080/10408398.2011.606928
Schilmiller AL, Stout J, Weng JK, Humphreys J, Ruegger MO, Chapple C (2009) Mutations in the cinnamate 4-hydroxylase gene impact metabolism, growth and development in Arabidopsis. Plant J 60:771–782. doi:10.1111/j.1365-313X.2009.03996.x
Shi JL, He MY, Cao JL, Wang H, Ding JH, Jiao YT, Li RM, He J, Wang D, Wang YJ (2014) The comparative analysis of the potential relationship between resveratrol and stilbene synthase gene family in the development stages of grapes (Vitis quinquangularis and Vitis vinifera). Plant Physiol Biochem 74:24–32. doi:10.1016/j.plaphy.2013.10.021
Shin SY, Han NS, Park YC, Kim MD, Seo JH (2011) Production of resveratrol from p-coumaric acid in recombinant Saccharomyces cerevisiae expressing 4-coumarate:coenzyme A ligase and stilbene synthase genes. Enzym Microb Technol 48:48–53. doi:10.1016/j.enzmictec.2010.09.004
Shin SY, Jung SM, Kim MD, Han NS, Seo JH (2012) Production of resveratrol from tyrosine in metabolically engineered Saccharomyces cerevisiae. Enzym Microb Technol 51:211–216. doi:10.1016/j.enzmictec.2012.06.005
Shrikanta A, Kumar A, Govindaswamy V (2015) Resveratrol content and antioxidant properties of underutilized fruits. J Food Sci Tech 52:383–390. doi:10.1007/s13197-013-0993-z
Shumakova OA, Manyakhin AY, Kiselev KV (2011) Resveratrol content and expression of phenylalanine ammonia-lyase and stilbene synthase genes in cell cultures of Vitis amurensis treated with coumaric acid. Appl Biochem Biotechnol 165:1427–1436. doi:10.1007/s12010-011-9361-5
Singh K, Kumar S, Rani A, Gulati A, Ahuja PS (2009) Phenylalanine ammonia-lyase (PAL) and cinnamate 4-hydroxylase (C4H) and catechins (flavan-3-ols) accumulation in tea. Funct Integr Genomics 9:125–134. doi:10.1007/s10142-008-0092-9
Soural I, Vrchotová N, Tříska J, Balík J, Horník Š, Cuřínová P, Sýkora J (2015) Various extraction methods for obtaining stilbenes from grape cane of Vitis vinifera L. Molecules 20:6093–6112. doi:10.3390/molecules20046093
Sun HY, Guo K, Feng SQ, Zou WH, Li Y, Fan CF, Peng LC (2015) Positive selection drives adaptive diversification of the 4-coumarate: CoA ligase (4CL) gene in angiosperms. Ecol Evol 5:3413–3420. doi:10.1002/ece3.1613
Suzuki S, Koeduka T, Sugiyama A, Yazaki K, Umezawa T (2014) Microbial production of plant specialized metabolites. Plant Biol 31:465–482. doi:10.5511/plantbiotechnology.14.1003a
Świeca M (2016) Hydrogen peroxide treatment and the phenylpropanoid pathway precursors feeding improve phenolics and antioxidant capacity of quinoa sprouts via an induction of L-tyrosine and L-phenylalanine ammonia-lyases activities. J Chem 2016:1–7. doi:10.1155/2016/1936516
Sydor T, Schaffer S, Boles E (2010) Considerable increase in resveratrol production by recombinant industrial yeast strains with use of rich medium. Appl Environ Microbiol 76:3361–3363. doi:10.1128/AEM.02796-09
Takaoka M (1940) Of the phenolic substances of white hellebore (Veratrum grandiflorum Loes. fil.). J Faculty Sci Hokkaido Imperial University 3:1–16. doi:10.1246/nikkashi1921.60.1261
Tantong S, Incharoensakdi A, Sirikantaramas S, Lindblad P (2016) Potential of Synechocystis PCC 6803 as a novel cyanobacterial chassis for heterologous expression of enzymes in the trans-resveratrol biosynthetic pathway. Protein Expr Purif 121:163–168. doi:10.1016/j.pep.2016.01.020
Tassoni A, Fornale S, Franceschetti M, Musiani F, Michael AJ, Perry B, Bagni N (2005) Jasmonates and Na-orthovanadate promote resveratrol production in Vitis vinifera cv. Barbera cell cultures. New Phytol 166:895–905. doi:10.1111/j.1469-8137.2005.01383.x
Tyunin AP, Kiselev KV (2015) Alternations in VaSTS gene cytosine methylation and t-resveratrol production in response to UV-C irradiation in Vitis amurensis Rupr. cells. Plant Cell Tiss Org 124:33–45. doi:10.1007/s11240-015-0872-6
Vandelle E, Poinssot B, Wendehenne D, Bentejac M, Pugin A (2006) Integrated signaling network involving calcium, nitric oxide, and active oxygen species but not mitogen-activated protein kinases in BcPG1-elicited grapevine defenses. Mol Plant-Microbe Interact 19:429–440. doi:10.1094/MPMI-19-0429
Vannelli T, Qi WW, Sweigard J, Gatenby AA, Sariaslani FS (2007) Production of p-hydroxycinnamic acid from glucose in Saccharomyces cerevisiae and Escherichia coli by expression of heterologous genes from plants and fungi. Metab Eng 9:142–151. doi:10.1016/j.ymben.2006.11.001
Vannozzi A, Dry IB, Fasoli M, Zenoni S, Lucchin M (2012) Genome-wide analysis of the grapevine stilbene synthase multigenic family: genomic organization and expression profiles upon biotic and abiotic stresses. BMC Plant Biol 12:1–22. doi:10.1186/1471-2229-12-130
Venugopalan A, Srivastava S (2015) Endophytes as in vitro production platforms of high value plant secondary metabolites. Biotechnol Adv 33:873–887. doi:10.1016/j.biotechadv.2015.07.004
Vuong TV, Franco C, Zhang W (2014) Treatment strategies for high resveratrol induction in Vitis vinifera L. cell suspension culture. Biol Reprod 1-2:15–21. doi:10.1016/j.btre.2014.04.002
Wang J, Guleria S, Koffas MA, Yan YJ (2016) Microbial production of value-added nutraceuticals. Curr Opin Biotechnol 37:97–104. doi:10.1016/j.copbio.2015.11.003
Wang JH, Cox DG, Ding WJ, Huang GH, Lin YC, Li CY (2014) Three new resveratrol derivatives from the mangrove endophytic fungus Alternaria sp. Mar Drugs 12:2840–2850. doi:10.3390/md12052840
Wang YC, Yu O (2012) Synthetic scaffolds increased resveratrol biosynthesis in engineered yeast cells. J Biotechnol 157:258–260. doi:10.1016/j.jbiotec.2011.11.003
Wang YC, Chen S, Yu O (2011a) Metabolic engineering of flavonoids in plants and microorganisms. Appl Microbiol Biotechnol 91:949–956. doi:10.1007/s00253-011-3449-2
Wang YC, Halls C, Zhang J, Matsuno M, Zhang YS, Yu O (2011b) Stepwise increase of resveratrol biosynthesis in yeast Saccharomyces cerevisiae by metabolic engineering. Metab Eng 13:455–463. doi:10.1016/j.ymben.2011.04.005
Wang YC, Yi H, Wang M, Yu O, Jez JM (2011c) Structural and kinetic analysis of the unnatural fusion protein 4-coumaroyl-CoA ligase::stilbene synthase. J Am Chem Soc 133:20684–20687. doi:10.1021/ja2085993
Watts KT, Mijts BN, Lee PC, Manning AJ, Schmidt-Dannert C (2006) Discovery of a substrate selectivity switch in tyrosine ammonia-lyase, a member of the aromatic amino acid lyase family. Chem Biol 13:1317–1326. doi:10.1016/j.chembiol.2006.10.008
Weitzel C, Petersen M (2010) Enzymes of phenylpropanoid metabolism in the important medicinal plant Melissa officinalis L. Planta 232:731–742. doi:10.1007/s00425-010-1206-x
Whitlock NC, Baek SJ (2012) The anticancer effects of resveratrol: modulation of transcription factors. Nutr Cancer 64:493–502. doi:10.1080/01635581.2012.667862
Wu JJ, Liu P, Fan YM, Bao H, GC D, Zhou JW, Chen J (2013) Multivariate modular metabolic engineering of Escherichia coli to produce resveratrol from L-tyrosine. J Biotechnol 167:404–411. doi:10.1016/j.jbiotec.2013.07.030
Xing BC, Yang DF, Guo WL, Liang ZS, Yan XJ, Zhu YH, Liu Y (2015) Ag+ as a more effective elicitor for production of tanshinones than phenolic acids in Salvia miltiorrhiza hairy roots. Molecules 20:309–324. doi:10.3390/molecules20010309
Xu A, Zhan JC, Huang WD (2015a) Combined elicitation of chitosan and ultraviolet C enhanced stilbene production and expression of chitinase and β-1,3-glucanase in Vitis vinifera cell suspension cultures. Plant Cell Tiss Org 124:105–117. doi:10.1007/s11240-015-0879-z
Xu A, Zhan JC, Huang WD (2015b) Oligochitosan and sodium alginate enhance stilbene production and induce defense responses in Vinifera cell suspension. Acta Physiol Plant 37:144–157. doi:10.1007/s11738-015-1900-1
Yang TH, Fang LL, Nopo-Olazabal C, Condori J, Nopo-Olazabal L, Balmaceda C, Medina-Bolivar F (2015) Enhanced production of resveratrol, piceatannol, arachidin-1, and arachidin-3 in hairy root cultures of peanut co-treated with methyl jasmonate and cyclodextrin. J Agric Food Chem 63:3942–3950. doi:10.1021/jf5050266
Zamboni A, Vrhovsek U, Kassemeyer HH, Mattivi F, Velasco R (2006) Elicitor-induced resveratrol production in cell cultures of different grape genotypes (Vitis spp.). Vitis 45:63–68
Zhang CH, Ma T, Luo WC, JM X, Liu JQ, Wan DS (2015a) Identification of 4CL genes in desert poplars and their changes in expression in response to salt stress. Genes 6:901–917. doi:10.3390/genes6030901
Zhang EH, Guo XF, Meng ZF, Wang J, Sun J, Yao X, Xun H (2015b) Construction, expression, and characterization of Arabidopsis thaliana 4CL and Arachis hypogaea RS fusion gene 4CL::RS in Escherichia coli. World J Microbiol Biotechnol 31:1379–1385. doi:10.1007/s11274-015-1889-z
Zhang J, Wang D, Pan JC, Wang J, Zhao HB, Li Q, Zhou XH (2014) Efficient resveratrol production by immobilized β-glucosidase on cross-linked chitosan microsphere modified by l-lysine. J Mol Catal B-Enzym 104:29–34. doi:10.1016/j.molcatb.2014.03.003
Zhang JH, Shi JL, Liu YL (2013a) Bioconversion of resveratrol using resting cells of non-genetically modified Alternaria sp. Biotechnol Appl Bioc 10:236–243. doi:10.1002/bab.1060
Zhang JH, Shi JL, Liu YL (2013b) Substrates and enzyme activities related to biotransformation of resveratrol from phenylalanine by Alternaria sp. MG1. Appl Microbiol Biotechnol 97:9941–9954. doi:10.1007/s00253-013-5212-3
Zhang YS, Li SZ, Li J, Pan XQ, Cahoon RE, Jaworski JG, Wang XM, Jez JM, Chen F, Yu O (2006) Using unnatural protein fusions to engineer resveratrol biosynthesis in yeast and mammalian cells. J Am Chem Soc 128:13030–13031. doi:10.1021/ja0622094
Zhao JL, Zhou LG, Wu JY (2010) Effects of biotic and abiotic elicitors on cell growth and tanshinone accumulation in Salvia miltiorrhiza cell cultures. Appl Microbiol Biotechnol 87:137–144. doi:10.1007/s00253-010-2443-4
Zhao YX, Xi Q, Xu Q, He MH, Ding JN, Dai YC, Keller NP, Zheng WF (2015) Correlation of nitric oxide produced by an inducible nitric oxide synthase-like protein with enhanced expression of the phenylpropanoid pathway in Inonotus obliquus cocultured with Phellinus morii. Appl Microbiol Biotechnol 99:4361–4372. doi:10.1007/s00253-014-6367-2
Acknowledgment
This review is supported by the National Key Technology R&D Program (No. 2015BAD16B02), the National Natural Science Fund (Grant No. 31471718), the Agriculture Department of China (Grant No. CARS-30), and the Northwestern Polytechnical University (No. 3102014JCQ15011 and No. 3102014GEKY1010).
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Lu, Y., Shao, D., Shi, J. et al. Strategies for enhancing resveratrol production and the expression of pathway enzymes. Appl Microbiol Biotechnol 100, 7407–7421 (2016). https://doi.org/10.1007/s00253-016-7723-1
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DOI: https://doi.org/10.1007/s00253-016-7723-1