Abstract
Main conclusion
β-carotene is biologically active compound widely distributed in plants. The use of plant in vitro cultures and genetic engineering is a promising strategy for its sustainable production.
Abstract
β-carotene is an orange carotenoid often found in leaves as well as in fruits, flowers, and roots. A member of the tetraterpene family, this 40-carbon isoprenoid has a conjugated double-bond structure, which is responsible for some of its most remarkable properties. In plants, β-carotene functions as an antenna pigment and antioxidant, providing protection against photooxidative damage caused by strong UV-B light. In humans, β-carotene acts as a precursor of vitamin A, prevents skin damage by solar radiation, and protects against several types of cancer such as oral, colon and prostate. Due to its wide spectrum of applications, the global market for β-carotene is expanding, and the demand can no longer be met by extraction from plant raw materials. Considerable research has been dedicated to finding more efficient production alternatives based on biotechnological systems. This review provides a detailed overview of the strategies used to increase the production of β-carotene in plant in vitro cultures, with particular focus on culture conditions, precursor feeding and elicitation, and the application of metabolic engineering.
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Data availability
All data analyzed during this study have been already published. Data sharing does not apply to this article as no datasets were generated during the current study.
References
Almagro L, Pedreño MA (2020) Use of cyclodextrins to improve the production of plant bioactive compounds. Phytochem Rev 19(4):1061–1080. https://doi.org/10.1007/s11101020-09704-6
Ampomah-Dwamena C, Driedonks N, Lewis D, Shumskaya M, Chen X, Wurtzel ET, Allan AC (2015) The Phytoene synthase gene family of apple (Malus x domestica) and its role in controlling fruit carotenoid content. BMC Plant Biol 15(1):1–14. https://doi.org/10.1007/s11101020-09704-6
Arab L, Steck-Scott S, Bowen P (2001) Participation of lycopene and beta-carotene in carcinogenesis: defenders, aggressors, or passive bystanders? Epidemiol Rev 23(2):211–230. https://doi.org/10.1093/oxfordjournals.epirev.a000803
Arango J, Wüst F, Beyer P, Welsch R (2010) Characterization of phytoene synthases from cassava and their involvement in abiotic stress-mediated responses. Planta 232(5):1251–1262. https://doi.org/10.1007/s00425-010-1250-6
Barreiro C, Barredo JL (2018) Carotenoid production: a healthy and profitable industry. Microbial Carotenoids. https://doi.org/10.1007/978-1-4939-8742-9_2
Bartley GE, Scolnik PA (1993) cDNA cloning, expression during development, and genome mapping of PSY2, a second tomato gene encoding phytoene synthase. J Biol Chem 268(34):25718–25721. https://doi.org/10.1016/S0021-9258(19)74448-2
BBResearch Report (2019) The Global Market for Carotenoids
Benítez-García I, Vanegas-Espinoza PE, Meléndez-Martínez AJ, Heredia FJ, Paredes-López O, Del Villar-Martínez AA (2014) Callus culture development of two varieties of Tagetes erecta and carotenoid production. Electron J Biotechnol 17(3):107–113. https://doi.org/10.1016/j.ejbt.2014.01.004
Cazzaniga S, Li Z, Niyogi KK, Bassi R, Dall’Osto L, (2012) The Arabidopsis szl1 mutant reveals a critical role of β-carotene in photosystem I photoprotection. Plant Physiol 159(4):1745–1758. https://doi.org/10.1104/pp.112.201137
Cazzonelli CI, Pogson BJ (2010) Source to sink: regulation of carotenoid biosynthesis in plants. Trends Plant Sci 15(5):266–274. https://doi.org/10.1016/j.tplants.2010.02.003
Chen CY, Kao AL, Tsai ZC, Shen YM, Kao PH, Ng IS, Chang JS (2017) Expression of synthetic phytoene synthase gene to enhance β-carotene production in Scenedesmus sp. CPC2. Biotechnol J 12(11):1700204. https://doi.org/10.1002/biot.201700204
da Rocha AS, Rocha EK, Alves LM, de Moraes BA, de Castro TC, Albarello N, Simões-Gurgel C (2015) Production and optimization through elicitation of carotenoid pigments in the in vitro cultures of Cleome rosea Vahl. (Cleomaceae). J Plant Biochem Biot 24(1):105–113. https://doi.org/10.1007/s13562-013-0241-7
Dias MG, Olmedilla-Alonso B, Hornero-Méndez D, Mercadante AZ, Osorio C, Vargas-Murga L, Meléndez-Martínez AJ (2018) Comprehensive database of carotenoid contents in Ibero-American foods. A valuable tool in the context of functional foods and the establishment of recommended intakes of bioactives. J Agric Food Chem 66:5055–5107. https://doi.org/10.1021/acs.jafc.7b06148
Dibari B, Murat F, Chosson A, Gautier V, Poncet C, Lecomte P, Salse J (2012) Deciphering the genomic structure, function and evolution of carotenogenesis related phytoene synthases in grasses. BMC Genom 13(1):1–14. https://doi.org/10.1186/1471-2164-13-221
Efferth T (2019) Biotechnology applications of plant callus cultures. Engineering 5(1):50–59. https://doi.org/10.1016/j.eng.2018.11.006
Eggersdorfer M, Wyss A (2018) Carotenoids in human nutrition and health. Arch Biochem Biophys 652:18–26. https://doi.org/10.1016/j.abb.2018.06.001
Engelmann NJ, Campbell JK, Rogers RB, Rupassara SI, Garlick PJ, Lila MA, Erdman JW Jr (2010) Screening and selection of high carotenoid producing in vitro tomato cell culture lines for [13C]-carotenoid production. J Agric Food Chem 58(18):9979–9987. https://doi.org/10.1021/jf101942x
Fantini E, Falcone G, Frusciante S, Giliberto L, Giuliano G (2013) Dissection of tomato lycopene biosynthesis through virus-induced gene silencing. Plant Physiol 163(2):986–998. https://doi.org/10.1104/pp.113.224733
Fraser PD, Romer S, Shipton CA, Mills PB, Kiano JW, Misawa N, Bramley PM (2002) Evaluation of transgenic tomato plants expressing an additional phytoene synthase in a fruit-specific manner. Proc Natl Acad Sci 99(2):1092–1097. https://doi.org/10.1073/pnas.241374598
Gamborg OL, Miller R, Ojima K (1968) Nutrient requirements of suspension cultures of soybean root cells. Exp Cell Res 50(1):151–158. https://doi.org/10.1016/0014-4827(68)90403-5
Gao H, Xu J, Liu X, Liu B, Deng X (2011) Light effect on carotenoids production and expression of carotenogenesis genes in citrus callus of four genotypes. Acta Physiol Plant 33(6):2485–2492. https://doi.org/10.1007/s11738-011-0793-x
Gonçalves S, Romano A (2018) Production of plant secondary metabolites by using biotechnological tools. Secondary metabolites, sources and applications. IntechOpen, pp 81–99. https://doi.org/10.5772/intechopen.76414
Grune T, Lietz G, Palou A, Ross AC, Stahl W, Tang G, Biesalski HK (2010) β-Carotene is an important vitamin A source for humans. J Nutr 140:2268S-2285S. https://doi.org/10.3945/jn.109.119024
Hanchinal VM, Survase SA, Sawant SK, Annapure US (2008) Response surface methodology in media optimization for production of β-carotene from Daucus carota. Plant Cell Tiss Org Cult 93(2):123–132. https://doi.org/10.1007/s11240-008-9350-8
Ho TT, Murthy HN, Park SY (2020) Methyl jasmonate induced oxidative stress and accumulation of secondary metabolites in plant cell and organ cultures. Int J Mol Sci 21(3):716. https://doi.org/10.3390/ijms21030716
Keasling JD (2010) Manufacturing molecules through metabolic engineering. Science 330:1355–1358. https://doi.org/10.1126/science.1193990
Kim SH, Ahn YO, Ahn MJ, Lee HS, Kwak SS (2012) Down-regulation of β-carotene hydroxylase increases β-carotene and total carotenoids enhancing salt stress tolerance in transgenic cultured cells of sweetpotato. Phytochemistry 74:69–78. https://doi.org/10.1016/j.phytochem.2011.11.003
Lee PC, Mijts BN, Schmidt-Dannert C (2004) Investigation of factors influencing production of the monocyclic carotenoid torulene in metabolically engineered Escherichia coli. Appl Microbiol Biotechnol 65(5):538–546. https://doi.org/10.1007/s00253-004-1619-1
Li F, Vallabhaneni R, Wurtzel ET (2008a) PSY3, a new member of the phytoene synthase gene family conserved in the Poaceae and regulator of abiotic stress-induced root carotenogenesis. Plant Physiol 146(3):1333–1345. https://doi.org/10.1104/pp.107.111120
Li F, Vallabhaneni R, Yu J, Rocheford T, Wurtzel ET (2008b) The maize phytoene synthase gene family: overlapping roles for carotenogenesis in endosperm, photomorphogenesis, and thermal stress tolerance. Plant Physiol 147(3):1334–1346. https://doi.org/10.1104/pp.108.122119
Liang MH, Lu Y, Chen HH, Jiang JG (2017) The salt-regulated element in the promoter of lycopene β-cyclase gene confers a salt regulatory pattern in carotenogenesis of Dunaliella bardawil. Environ Microbiol 19(3):982–989
Maass D, Arango J, Wüst F, Beyer P, Welsch R (2009) Carotenoid crystal formation in Arabidopsis and carrot roots caused by increased phytoene synthase protein levels. PLoS ONE 4(7):e6373. https://doi.org/10.1371/journal.pone.0006373
Marchev AS, Yordanova ZP, Georgiev MI (2020) Green (cell) factories for advanced production of plant secondary metabolites. Crit Rev Biotechnol 40(4):443–458. https://doi.org/10.1080/07388551.2020.1731414
Miclea I, Suhani A, Zahan M, Bunea A (2020) Effect of jasmonic acid and salicylic acid on growth and biochemical composition of in-vitro-propagated Lavandula angustifolia Mill. Agronomy 10(11):1722. https://doi.org/10.3390/agronomy10111722
Miras-Moreno B, Almagro L, Pedreño MA, Sabater-Jara AB (2016) Enhanced accumulation of phytosterols and phenolic compounds in cyclodextrin-elicited cell suspension culture of Daucus carota. Plant Sci 250:154–164. https://doi.org/10.1016/j.plantsci.2016.06.008
Miras-Moreno B, Pedreño MA, Fraser PD, Sabater-Jara AB, Almagro L (2019) Effect of diflufenican on total carotenoid and phytoene production in carrot suspension-cultured cells. Planta 249(1):113–122. https://doi.org/10.1007/s00425-018-2966-y
Mohanlall V (2020) Plant cell culture systems for the production of secondary metabolites: a review. IOSR-JBB. https://doi.org/10.9790/264X-0601023547
Molino A, Larocca V, Di Sanzo G, Martino M, Casella P, Marino T, Karatza D, Musmarra D (2019) Extraction of bioactive compounds using supercritical carbon dioxide. Molecules 24:782–799. https://doi.org/10.3390/molecules24040782
Moses T, Pollier J, Thevelein JM, Goossens A (2013) Bioengineering of plant (tri) terpenoids: from metabolic engineering of plants to synthetic biology in vivo and in vitro. New Phytol 200(1):27–43. https://doi.org/10.1111/nph.12325
Murashige T, Skoog F (1962) A revised medium for rapid growth and bioassays with tobacco tissue cultures. Physiol Plant 15(3):473–497. https://doi.org/10.1111/j.1399-3054.1962.tb08052.x
Oleszkiewicz T, Kruczek M, Baranski R (2021) Repression of carotenoid accumulation by nitrogen and NH4+ supply in carrot callus cells in vitro. Plants 10(9):1813. https://doi.org/10.3390/plants10091813
Olgunsoy P, Ulusoy S, Çelikkol Akçay U (2017) Metabolite production and antibacterial activities of callus cultures from Rosa damascena Mill. Petals. Marmara Pharm J 21(3):590–590. https://doi.org/10.12991/marupj.319331
Otani M, Kitayama K, Ishikuro H, Hattan JI, Maoka T, Harada H, Misawa N (2021) Construction of transgenic Ipomoea obscura that exhibits new reddish leaf and flower colors due to introduction of β-carotene ketolase and hydroxylase genes. Plant Biotechnol. https://doi.org/10.5511/plantbiotechnology.21.0309a
Park HY, Saini RK, Gopal J, Keum YS, Kim DH, Lee O, Sivanesan I (2017) Micropropagation and subsequent enrichment of carotenoids, fatty acids, and tocopherol contents in Sedum dasyphyllum L. Front Chem 5:77–87. https://doi.org/10.3389/fchem.2017.00077
Rizzello F, De Paolis A, Durante M, Blando F, Mita G, Caretto S (2014) Enhanced production of bioactive isoprenoid compounds from cell suspension cultures of Artemisia annua L. using β-cyclodextrins. Int J Mol Sci 15(10):19092–19105. https://doi.org/10.3390/ijms151019092
Rodriguez-Concepcion M, Stange C (2013) Biosynthesis of carotenoids in carrot: an underground story comes to light. Arch Biochem Biophys 539(2):110–116. https://doi.org/10.1016/j.abb.2013.07.009
Rodriguez-Concepcion M, Avalos J, Bonet ML, Boronat A, Gomez-Gomez L, Hornero-Mendez D, Limón MC, Melendez-Martínez AJ, Olmedilla-Alonso B, Palou A, Ribot J, Rodrigo MJ, Zacarias L, Zhu C (2018) A global perspective on carotenoids: metabolism, biotechnology, and benefits for nutrition and health. Prog Lipid Res 70:62–93
Saeed B, Das M, Khurana P (2015) Overexpression of β-carotene hydroxylase1 (BCH1) in Indian mulberry, Morus indica cv. K2, confers tolerance against UV, high temperature and high irradiance stress induced oxidative damage. Plant Cell Tiss Org Cult 120(3):1003–1014. https://doi.org/10.1007/s11240-014-0654-6
Sathasivam R, Ki JS (2018) A review of the biological activities of microalgal carotenoids and their potential use in healthcare and cosmetic industries. Mar Drugs 16(1):26–57. https://doi.org/10.3390/md16010026
Shahbazi M, Gilbert M, Labouré AM, Kuntz M (2007) Dual role of the plastid terminal oxidase in tomato. Plant Physiol 145(3):691–702. https://doi.org/10.1104/pp.107.106336
Shimizu K, Kikuchi T, Sugano N, Nishi A (1979) Carotenoid and steroid syntheses by carrot cells in suspension culture. Physiol Plant 46(2):127–132. https://doi.org/10.1111/j.1399-3054.1979.tb06544.x
Torres-Montilla S, Rodriguez-Concepcion M (2021) Making extra room for carotenoids in plant cells: new opportunities for biofortification. Prog Lipid Res 84:101128–101137. https://doi.org/10.1016/j.plipres.2021.101128
Tran D, Haven J, Qiu WG, Polle JE (2009) An update on carotenoid biosynthesis in algae: phylogenetic evidence for the existence of two classes of phytoene synthase. Planta 229(3):723–729. https://doi.org/10.1007/s00425-008-0866-2
Von Lintig J, Welsch R, Bonk M, Giuliano G, Batschauer A, Kleinig H (1997) Light dependent regulation of carotenoid biosynthesis occurs at the level of phytoene synthase expression and is mediated by phytochrome in Sinapis alba and Arabidopsis thaliana seedlings. Plant J 12(3):625–634. https://doi.org/10.1046/j.1365-313x.1997.00625.x
Wang J, Hu X, Chen J, Wang T, Huang X, Chen G (2022) The extraction of β-carotene from microalgae for testing their health benefits. Foods 11:502–521. https://doi.org/10.3390/foods11040502
Welsch R, Medina J, Giuliano G, Beyer P, Von Lintig J (2003) Structural and functional characterization of the phytoene synthase promoter from Arabidopsis thaliana. Planta 216(3):523–534. https://doi.org/10.1007/s00425-002-0885-3
Welsch R, Wust F, Bar C, Al-Babili S, Beyer P (2008) A third phytoene synthase is devoted to abiotic stress-induced abscisic acid formation in rice and defines functional diversification of phytoene synthase genes. Plant Physiol 147(1):367–380. https://doi.org/10.1104/pp.108.117028
Zare M, Norouzi Roshan Z, Assadpour E, Jafari SM (2021) Improving the cancer prevention/treatment role of carotenoids through various nano-delivery systems. Crit Rev Food Sci Nut 61(3):522–534. https://doi.org/10.1080/10408398.2020.1738999
Zhu C, Bai C, Sanahuja G, Yuan D, Farré G, Naqvi S, Christou P (2010) The regulation of carotenoid pigmentation in flowers. Arch Biochem Biophys 504(1):132–141. https://doi.org/10.1016/j.abb.2010.07.028
Acknowledgements
This research was part of the project PID2020-113438RB-I00 financed by Ministerio de Ciencia e Innovación (Spain) (MCIN/ AEI/10.13039/501100011033 “Una manera de hacer Europa”).
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Almagro, L., Correa-Sabater, J.M., Sabater-Jara, A.B. et al. Biotechnological production of β-carotene using plant in vitro cultures. Planta 256, 41 (2022). https://doi.org/10.1007/s00425-022-03953-9
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DOI: https://doi.org/10.1007/s00425-022-03953-9