{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T06:25:32Z","timestamp":1775197532276,"version":"3.50.1"},"reference-count":110,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,8,15]],"date-time":"2020-08-15T00:00:00Z","timestamp":1597449600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia, Portugal","award":["UIDB\/04551\/2020"],"award-info":[{"award-number":["UIDB\/04551\/2020"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia, Portugal","award":["LISBOA-01-0145-FEDER-007660"],"award-info":[{"award-number":["LISBOA-01-0145-FEDER-007660"]}]},{"name":"NUI Galway Research Grant for Returning Academic Careers","award":["QA151"],"award-info":[{"award-number":["QA151"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Plants"],"abstract":"<jats:p>Carotenoids are a class of pigments with a biological role in light capture and antioxidant activities. High value ketocarotenoids, such as astaxanthin and canthaxanthin, are highly appealing for applications in human nutraceutical, cosmetic, and animal feed industries due to their color- and health-related properties. In this review, recent advances in metabolic engineering and synthetic biology towards the production of ketocarotenoids, in particular the red-orange canthaxanthin, are highlighted. Also reviewed and discussed are the properties of canthaxanthin, its natural producers, and various strategies for its chemical synthesis. We review the de novo synthesis of canthaxanthin and the functional \u03b2-carotene ketolase enzyme across organisms, supported by a protein-sequence-based phylogenetic analysis. Various possible modifications of the carotenoid biosynthesis pathway and the present sustainable cost-effective alternative platforms for ketocarotenoids biosynthesis are also discussed.<\/jats:p>","DOI":"10.3390\/plants9081039","type":"journal-article","created":{"date-parts":[[2020,8,17]],"date-time":"2020-08-17T04:35:51Z","timestamp":1597638951000},"page":"1039","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":93,"title":["Canthaxanthin, a Red-Hot Carotenoid: Applications, Synthesis, and Biosynthetic Evolution"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3771-1482","authenticated-orcid":false,"given":"B\u00e1rbara A.","family":"Rebelo","sequence":"first","affiliation":[{"name":"Plant Cell Biology Laboratory, Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier (ITQB NOVA), Universidade Nova de Lisboa, 2780-157 Oeiras, Portugal"},{"name":"Bioorganic Chemistry Laboratory, Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier (ITQB NOVA), Universidade Nova de Lisboa, 2780-157 Oeiras, Portugal"}]},{"given":"Sara","family":"Farrona","sequence":"additional","affiliation":[{"name":"Plant and AgriBiosciences Centre, Ryan Institute, NUI Galway, H19 TK33 Galway, Ireland"}]},{"given":"M. Rita","family":"Ventura","sequence":"additional","affiliation":[{"name":"Bioorganic Chemistry Laboratory, Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier (ITQB NOVA), Universidade Nova de Lisboa, 2780-157 Oeiras, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3173-3701","authenticated-orcid":false,"given":"Rita","family":"Abranches","sequence":"additional","affiliation":[{"name":"Plant Cell Biology Laboratory, Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier (ITQB NOVA), Universidade Nova de Lisboa, 2780-157 Oeiras, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e0158","DOI":"10.1199\/tab.0158","article-title":"Carotenoid biosynthesis in Arabidopsis: A colorful pathway","volume":"10","year":"2012","journal-title":"Arab. Book"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4810","DOI":"10.3390\/md12094810","article-title":"Synthetic biology and metabolic engineering for marine carotenoids: New opportunities and future prospects","volume":"12","author":"Wang","year":"2014","journal-title":"Mar. Drugs"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.abb.2008.10.029","article-title":"Metabolic engineering of ketocarotenoid biosynthesis in higher plants","volume":"483","author":"Zhu","year":"2009","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1111\/pbi.12365","article-title":"Product stability and sequestration mechanisms in Solanum tuberosum engineered to biosynthesize high value ketocarotenoids","volume":"14","author":"Mortimer","year":"2016","journal-title":"Plant Biotechnol. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.jplph.2005.06.003","article-title":"Preferential inhibition of the lycopene \u03b5-cyclase by the substituted triethylamine compound MPTA in higher plants","volume":"163","author":"Phillip","year":"2006","journal-title":"J. Plant Physiol."},{"key":"ref_6","first-page":"125","article-title":"Biotechnological production of carotenoids and their applications in food and pharmaceutical products","volume":"Volume 8","author":"Cvetkovic","year":"2017","journal-title":"Carotenoids"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3055","DOI":"10.1105\/tpc.111.086827","article-title":"Elucidation of the Pathway to Astaxanthin in the Flowers of Adonis aestivalis","volume":"23","author":"Cunningham","year":"2011","journal-title":"Plant Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"38","DOI":"10.12944\/CRNFSJ.4.Special-Issue1.04","article-title":"Carotenoids: From plants to food industry","volume":"4","author":"Zakynthinos","year":"2016","journal-title":"Curr. Res. Nutr. Food Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"237","DOI":"10.4014\/jmb.1203.03032","article-title":"Characterization of canthaxanthin isomers isolated from a new soil Dietzia sp. and their antioxidant activities","volume":"23","author":"Venugopalan","year":"2013","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1016\/j.foodchem.2006.03.015","article-title":"Relationship between the colour and the chemical structure of carotenoid pigments","volume":"101","author":"Britton","year":"2007","journal-title":"Food Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1007\/s12161-013-9660-2","article-title":"Identification of the Composition of Isomeric Canthaxanthin Sample by NMR, HPLC, and Mass Spectrometry","volume":"7","author":"Qiu","year":"2014","journal-title":"Food Anal. Methods"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/S0021-9673(01)84577-5","article-title":"Isolation of cis-trans isomers of canthaxanthin by high-performance liquid chromatography using a calcium hydroxide column and identification of their configurations by 1H NMR spectroscopy","volume":"448","author":"Hashimoto","year":"1988","journal-title":"J. Chromatogr. A"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.plipres.2018.04.004","article-title":"A global perspective on carotenoids: Metabolism, biotechnology, and benefits for nutrition and health","volume":"70","author":"Avalos","year":"2018","journal-title":"Prog. Lipid Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.plipres.2003.10.002","article-title":"The biosynthesis and nutritional uses of carotenoids","volume":"43","author":"Fraser","year":"2004","journal-title":"Prog. Lipid Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1475-2859-7-3","article-title":"Conversion of \u03b2-carotene into astaxanthin: Two separate enzymes or a bifunctional hydroxylase-ketolase protein?","volume":"7","author":"Barredo","year":"2008","journal-title":"Microb. Cell Fact."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/mnfr.201600469","article-title":"Canthaxanthin: From molecule to function","volume":"61","author":"Esatbeyoglu","year":"2017","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.foodres.2011.06.007","article-title":"Carotenoids bioavailability from foods: From plant pigments to efficient biological activities","volume":"46","year":"2012","journal-title":"Food Res. Int."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1021\/jf001169z","article-title":"Analysis of canthaxanthin and related pigments from Gordonia jacobaea mutants","volume":"49","author":"Sieiro","year":"2001","journal-title":"J. Agric. Food Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/j.foodchem.2005.10.026","article-title":"Accumulation and antioxidant activity of secondary carotenoids in the aerial microalga Coelastrella striolata var","volume":"100","author":"Abe","year":"2007","journal-title":"multistriata. Food Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1146\/annurev.nutr.22.010402.102834","article-title":"Carotenoid bioavailability and bioconversion","volume":"22","author":"Yeum","year":"2002","journal-title":"Annu. Rev. Nutr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1080\/10942910601045271","article-title":"Functional properties of carotenoids in human health","volume":"10","author":"Perera","year":"2007","journal-title":"Int. J. Food Prop."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Reboul, E. (2019). Mechanisms of Carotenoid Intestinal Absorption: Where Do We Stand?. Nutrients, 11.","DOI":"10.3390\/nu11040838"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.freeradbiomed.2013.07.025","article-title":"Regulation of the Nrf2 antioxidant pathway by microRNAs: New players in micromanaging redox homeostasis","volume":"64","author":"Cheng","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e17023","DOI":"10.1038\/sigtrans.2017.23","article-title":"NF-\u03baB signaling in inflammation","volume":"2","author":"Liu","year":"2017","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5733","DOI":"10.1021\/acs.jafc.8b00866","article-title":"Dietary Carotenoid Roles in Redox Homeostasis and Human Health","volume":"66","author":"Barros","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/s41580-020-0230-3","article-title":"Reactive oxygen species (ROS) as pleiotropic physiological signalling agents","volume":"21","author":"Sies","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/S0003-9861(03)00014-6","article-title":"Singlet oxygen quenching by dietary carotenoids in a model membrane environment","volume":"412","author":"Cantrell","year":"2003","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1093\/carcin\/19.3.403","article-title":"Dietary carotenoids inhibit aflatoxin B1-induced liver preneoplastic foci and DNA damage in the rat: Role of the modulation of aflatoxin B1 metabolism","volume":"19","author":"Gradelet","year":"1998","journal-title":"Carcinogenesis"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1080\/15287394.2019.1648346","article-title":"Effects of astaxanthin and canthaxanthin on oxidative stress biomarkers in rainbow trout","volume":"82","author":"Elia","year":"2019","journal-title":"J. Toxicol. Environ. Health Part A Curr. Issues"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/0003-9861(92)90675-M","article-title":"Astaxanthin and canthaxanthin are potent antioxidants in a membrane model","volume":"297","author":"Palozza","year":"1992","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"395","DOI":"10.2478\/s11658-009-0010-8","article-title":"Interactions between canthaxanthin and lipid membranes\u2014Possible mechanisms of canthaxanthin toxicity","volume":"14","author":"Sujak","year":"2009","journal-title":"Cell. Mol. Biol. Lett."},{"key":"ref_32","unstructured":"(2020, July 10). Carotenoids Market by Product, Source, and Application: Global Opportunity Analysis and Industry Forecast, 2018\u20132025. Available online: www.alliedmarketresearch.com\/press-release\/carotenoids-market.htm."},{"key":"ref_33","unstructured":"(2020, August 07). Carotenoids Market Size by Source (Natural, Synthetic), by Product (Beta-Carotene, Lutein, Astaxanthin, Canthaxanthin, Lycopene), by Application (Food & Beverages, Pharmaceutical, Cosmetics, Animal Feed, Dietary Supplements), Industry Analysis Report, Reg. Available online: https:\/\/www.gminsights.com\/industry-analysis\/carotenoids-market."},{"key":"ref_34","unstructured":"(2020, August 07). Canthaxanthin Market Size by Source (Synthetic, Natural), by Application (Dietary Supplement, Personal Care, Pharmaceuticals, Food & Beverages, Animal Feed {Aquaculture, Livestock, Pets}), Industry Analysis Report, Regional Outlook, Growth Potential, Pric. Available online: https:\/\/www.gminsights.com\/industry-analysis\/canthaxanthin-market."},{"key":"ref_35","unstructured":"(2020, August 07). Global Canthaxanthin Market to Exceed $85 mn by 2024. Available online: https:\/\/www.gminsights.com\/pressrelease\/canthaxanthin-market."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1086\/335653","article-title":"Carotenoids of the Mushroom Cantharellus cinnabarinus","volume":"112","author":"Haxo","year":"1950","journal-title":"Bot. Gaz."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"7598","DOI":"10.1016\/j.biortech.2010.04.093","article-title":"Extraction, purification and concentration of partially saturated canthaxanthin from Aspergillus carbonarius","volume":"101","author":"Krupa","year":"2010","journal-title":"Bioresour. Technol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S0032-9592(97)00045-9","article-title":"Optimization of carotenoid production by Phaffia rhodozyma cells grown on xylose","volume":"33","author":"Santos","year":"1998","journal-title":"Process Biochem."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Barredo, J., Garc\u00eda-Estrada, C., Kosalkova, K., and Barreiro, C. (2017). Biosynthesis of Astaxanthin as a Main Carotenoid in the Heterobasidiomycetous Yeast Xanthophyllomyces dendrorhous. J. Fungi, 3.","DOI":"10.3390\/jof3030044"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Singh, D.P., Khattar, J.S., Rajput, A., Chaudhary, R., and Singh, R. (2019). High production of carotenoids by the green microalga Asterarcys quadricellulare PUMCC 5.1.1 under optimized culture conditions. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0221930"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/0305-1978(89)90001-X","article-title":"Primary and secondary carotenoids in two races of the green alga Botryococcus braunii","volume":"17","author":"Grung","year":"1989","journal-title":"Biochem. Syst. Ecol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1111\/j.1399-3054.1993.tb00148.x","article-title":"Accumulation of canthaxanthin in Chlorella emersonii","volume":"87","author":"Malis","year":"1993","journal-title":"Physiol. Plant."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/0960-8524(96)00058-2","article-title":"Evolution of pigment composition in Chlorella vulgaris","volume":"57","author":"Gouveia","year":"1996","journal-title":"Bioresour. Technol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/S0176-1617(11)82019-5","article-title":"(Malis) Pigment and Structural Changes in Chlorella zofingiensis upon Light and Nitrogen Stress","volume":"146","author":"Bar","year":"1995","journal-title":"J. Plant Physiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1002\/jssc.200500365","article-title":"Isolation and purification of canthaxanthin from the microalga Chlorella zofingiensis by high-speed counter-current chromatography","volume":"29","author":"Li","year":"2006","journal-title":"J. Sep. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S0308-8146(01)00279-5","article-title":"Carotenoid composition in the green microalga Chlorococcum","volume":"76","author":"Yuan","year":"2002","journal-title":"Food Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.biortech.2013.10.073","article-title":"Induction of canthaxanthin production in a Dactylococcus microalga isolated from the Algerian Sahara","volume":"151","author":"Grama","year":"2014","journal-title":"Bioresour. Technol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1042\/bj1010735","article-title":"Isolation and identification of carotenoids produced by a green alga (Dictyococcus cinnabarinus) in submerged culture","volume":"101","author":"Romagnoli","year":"1966","journal-title":"Biochem. J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/0044-8486(93)90447-7","article-title":"Carotenoid pigments of the green alga Haematococcus pluvialis: Assay on rainbow trout, Oncorhynchus mykiss, pigmentation in comparison with synthetic astaxanthin and canthaxanthin","volume":"112","author":"Choubert","year":"1993","journal-title":"Aquaculture"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1007\/s00217-006-0270-8","article-title":"Supercritical carbon dioxide extraction of astaxanthin and other carotenoids from the microalga Haematococcus pluvialis","volume":"223","author":"Nobre","year":"2006","journal-title":"Eur. Food Res. Technol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Shah, M.M.R., Liang, Y., Cheng, J.J., and Daroch, M. (2016). Astaxanthin-producing green microalga Haematococcus pluvialis: From single cell to high value commercial products. Front. Plant Sci., 7.","DOI":"10.3389\/fpls.2016.00531"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1023\/A:1008170915932","article-title":"Nannochloropsis (Eustigmatophyceae) as source of commercially valuable pigments","volume":"12","author":"Montero","year":"2000","journal-title":"J. Appl. Phycol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/j.procbio.2008.03.010","article-title":"The accumulation and metabolism of astaxanthin in Scenedesmus obliquus (Chlorophyceae)","volume":"43","author":"Qin","year":"2008","journal-title":"Process Biochem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1128\/aem.63.3.1151-1154.1997","article-title":"Identification of the carotenoid pigment canthaxanthin from photosynthetic Bradyrhizobium strains","volume":"63","author":"Lorquin","year":"1997","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2505","DOI":"10.1128\/aem.55.10.2505-2510.1989","article-title":"Reinvestigation of Brevibacterium sp. Strain KY-4313 as a Source of Canthaxanthin","volume":"55","author":"Nelis","year":"1989","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1590\/S0104-66322010000400003","article-title":"Enhancement of canthaxanthin production from Dietzia natronolimnaea HS-1 in a fed-batch process using trace elements and statistical methods","volume":"27","author":"Nasrabadi","year":"2010","journal-title":"Braz. J. Chem. Eng."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2134","DOI":"10.1007\/s13197-012-0713-0","article-title":"Stabilization of canthaxanthin produced by Dietzia natronolimnaea HS-1 with spray drying microencapsulation","volume":"51","author":"Hojjati","year":"2014","journal-title":"J. Food Sci. Technol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1128\/jb.92.2.342-345.1966","article-title":"Isolation and Identification of Canthaxanthin from Micrococcus roseus","volume":"92","author":"Cooney","year":"1966","journal-title":"J. Bacteriol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1128\/jb.96.1.234-241.1968","article-title":"Isolation and characterization of carotenoid pigments of Micrococcus roseus","volume":"96","author":"Ungers","year":"1968","journal-title":"J. Bacteriol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1021\/np060365i","article-title":"Major carotenoid isolated from Paracoccus schoinia NBRC 100637T is adonixanthin diglucoside","volume":"69","author":"Takaichi","year":"2006","journal-title":"J. Nat. Prod."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1016\/S1389-1723(00)87089-9","article-title":"Production of canthaxanthin by extremely halophilic bacteria","volume":"88","author":"Asker","year":"1999","journal-title":"J. Biosci. Bioeng."},{"key":"ref_62","first-page":"729","article-title":"Haloferax alexandrinus sp. nov., an extremely halophilic canthaxanthin-producing archaeon from a solar saltern in Alexandria (Egypt)","volume":"52","author":"Asker","year":"2002","journal-title":"Int. J. Syst. Evol. Microbiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.tifs.2007.04.009","article-title":"Modern application of xanthophylls in animal feeding\u2014A review","volume":"18","author":"Breithaupt","year":"2007","journal-title":"Trends Food Sci. Technol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1351\/pac198557050741","article-title":"Synthetic advances in the carotenoid field","volume":"57","author":"Widmer","year":"1985","journal-title":"Pure Appl. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2130","DOI":"10.1021\/jo00132a028","article-title":"Canthaxanthin. A new total synthesis","volume":"47","author":"Rosenberger","year":"1982","journal-title":"J. Org. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3328","DOI":"10.1021\/jo050101l","article-title":"Efficient syntheses of the Keto-carotenoids Canthaxanthin, Astaxanthin, and Astacene","volume":"70","author":"Choi","year":"2005","journal-title":"J. Org. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/s13738-019-01784-2","article-title":"Practical synthesis of canthaxanthin","volume":"17","author":"Pi","year":"2020","journal-title":"J. Iran. Chem. Soc."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.phytochem.2009.10.011","article-title":"Over-expression of Arabidopsis thaliana carotenoid hydroxylases individually and in combination with a \u03b2-carotene ketolase provides insight into in vivo functions","volume":"71","author":"Kim","year":"2010","journal-title":"Phytochemistry"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.pbi.2014.05.006","article-title":"Plant carotenoids: Genomics meets multi-gene engineering","volume":"19","author":"Giuliano","year":"2014","journal-title":"Curr. Opin. Plant Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1111\/tpj.12283","article-title":"Three distinct mutational mechanisms acting on a single gene underpin the origin of yellow flesh in peach","volume":"76","author":"Falchi","year":"2013","journal-title":"Plant J."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Pierce, E.C., LaFayette, P.R., Ortega, M.A., Joyce, B.L., Kopsell, D.A., and Parrott, W.A. (2015). Ketocarotenoid production in soybean seeds through metabolic engineering. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0138196"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"8419","DOI":"10.1007\/s00253-015-6791-y","article-title":"Highly efficient biosynthesis of astaxanthin in Saccharomyces cerevisiae by integration and tuning of algal crtZ and bkt","volume":"99","author":"Zhou","year":"2015","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1021\/acs.jafc.8b05003","article-title":"Directed coevolution of \u03b2-Carotene Ketolase and Hydroxylase and its application in temperature-regulated biosynthesis of Astaxanthin","volume":"67","author":"Zhou","year":"2019","journal-title":"J. Agric. Food Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1039\/c0np00036a","article-title":"Carotenoids and their cleavage products: Biosynthesis and functions","volume":"28","author":"Walter","year":"2011","journal-title":"Nat. Prod. Rep."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1126\/science.1143609","article-title":"The Chlamydomonas genome reveals the evolution of key animal and plant functions","volume":"318","author":"Merchant","year":"2007","journal-title":"Science"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Perozeni, F., Cazzaniga, S., Baier, T., Zanoni, F., Zoccatelli, G., Lauersen, K.J., Wobbe, L., and Ballottari, M. (2020). Turning a green alga red: Engineering astaxanthin biosynthesis by intragenic pseudogene revival in Chlamydomonas reinhardtii. Plant Biotecnhol. J., 1\u201315.","DOI":"10.1101\/535989"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2500","DOI":"10.1016\/j.procbio.2012.10.012","article-title":"Progress toward an Escherichia coli canthaxanthin bioprocess","volume":"47","author":"Scaife","year":"2012","journal-title":"Process Biochem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1007\/s10126-004-5100-z","article-title":"Characterization of \u03b2-carotene ketolases, CrtW, from marine bacteria by complementation analysis in Escherichia coli","volume":"7","author":"Choi","year":"2005","journal-title":"Mar. Biotechnol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"126455","DOI":"10.1016\/j.micres.2020.126455","article-title":"Improved production of echinenone and canthaxanthin in transgenic Nostoc sp. PCC 7120 overexpressing a heterologous crtO gene from Nostoc flagelliforme","volume":"236","author":"Gao","year":"2020","journal-title":"Microbiol. Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.ymben.2018.12.006","article-title":"Construction of a fusion enzyme for astaxanthin formation and its characterisation in microbial and plant hosts: A new tool for engineering ketocarotenoids","volume":"52","author":"Nogueira","year":"2019","journal-title":"Metab. Eng."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1111\/j.1365-313X.2008.03559.x","article-title":"Biosynthesis of astaxanthin in tobacco leaves by transplastomic engineering","volume":"55","author":"Hasunuma","year":"2008","journal-title":"Plant J."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1016\/j.molp.2018.09.007","article-title":"From Golden Rice to aSTARice: Bioengineering Astaxanthin Biosynthesis in Rice Endosperm","volume":"11","author":"Zhu","year":"2018","journal-title":"Mol. Plant"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1093\/jxb\/erp006","article-title":"Pathway engineering of Brassica napus seeds using multiple key enzyme genes involved in ketocarotenoid formation","volume":"60","author":"Fujisawa","year":"2009","journal-title":"J. Exp. Bot."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1007\/s11248-007-9120-0","article-title":"Metabolic engineering of novel ketocarotenoid production in carrot plants","volume":"17","author":"Jayaraj","year":"2008","journal-title":"Transgenic Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.ymben.2013.02.005","article-title":"Metabolic engineering of tomato for high-yield production of astaxanthin","volume":"17","author":"Huang","year":"2013","journal-title":"Metab. Eng."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"10876","DOI":"10.1073\/pnas.1708349114","article-title":"Engineering of tomato for the sustainable production of ketocarotenoids and its evaluation in aquaculture feed","volume":"114","author":"Nogueira","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/s11816-010-0147-y","article-title":"Metabolic engineering of Lilium \u00d7 formolongi using multiple genes of the carotenoid biosynthesis pathway","volume":"4","author":"Azadi","year":"2010","journal-title":"Plant Biotechnol. Rep."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"4937","DOI":"10.1007\/s00253-012-4610-2","article-title":"Canthaxanthin production with modified Mucor circinelloides strains","volume":"97","author":"Papp","year":"2013","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S1096-7176(03)00008-9","article-title":"Review of the BRENDA Database","volume":"5","author":"Pharkya","year":"2003","journal-title":"Metab. Eng."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Holliday, G.L., Brown, S.D., Mischel, D., Polacco, B.J., and Babbitt, P.C. (2020). A strategy for large-scale comparison of evolutionary- and reaction-based classifications of enzyme function. Database, 2020.","DOI":"10.1093\/database\/baaa034"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"9728","DOI":"10.1074\/jbc.272.15.9728","article-title":"A new type of asymmetrically acting \u03b2-carotene ketolase is required for the synthesis of echinenone in the cyanobacterium Synechocystis sp. PCC 6803","volume":"272","author":"Sandmann","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s13131-018-1178-4","article-title":"Phylogenetic analyses of the genes involved in carotenoid biosynthesis in algae","volume":"37","author":"Wang","year":"2018","journal-title":"Acta Oceanol. Sin."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.tifs.2019.08.016","article-title":"De novo synthesis of astaxanthin: From organisms to genes","volume":"92","author":"Fang","year":"2019","journal-title":"Trends Food Sci. Technol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1093\/molbev\/msy096","article-title":"MEGA X: Molecular evolutionary genetics analysis across computing platforms","volume":"35","author":"Kumar","year":"2018","journal-title":"Mol. Biol. Evol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"D265","DOI":"10.1093\/nar\/gkz991","article-title":"CDD\/SPARCLE: The conserved domain database in 2020","volume":"48","author":"Lu","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"D427","DOI":"10.1093\/nar\/gky995","article-title":"The Pfam protein families database in 2019","volume":"47","author":"Mistry","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1016\/j.febslet.2005.02.066","article-title":"The cyanobacterium Gloeobacter violaceus PCC 7421 uses bacterial-type phytoene desaturase in carotenoid biosynthesis","volume":"579","author":"Tsuchiya","year":"2005","journal-title":"FEBS Lett."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/s00203-005-0004-5","article-title":"Carotenoid biosynthesis in Gloeobacter violaceus PCC4721 involves a single crtI-type phytoene desaturase instead of typical cyanobacterial enzymes","volume":"184","author":"Steiger","year":"2005","journal-title":"Arch. Microbiol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"757","DOI":"10.3390\/md9050757","article-title":"Carotenoid \u03b2-ring hydroxylase and ketolase from marine bacteria\u2014Promiscuous enzymes for synthesizing functional xanthophylls","volume":"9","author":"Misawa","year":"2011","journal-title":"Mar. Drugs"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1023\/B:BILE.0000025880.91269.cf","article-title":"Cloning of two carotenoid ketolase genes from Nostoc punctiforme for the heterologous production of canthaxanthin and astaxanthin","volume":"26","author":"Steiger","year":"2004","journal-title":"Biotechnol. Lett."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"197","DOI":"10.7150\/ijbs.2.197","article-title":"Carotenoid biosynthesis in cyanobacteria: Structural and evolutionary scenarios based on comparative genomics","volume":"2","author":"Liang","year":"2006","journal-title":"Int. J. Biol. Sci."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Enfissi, E.M.A., Nogueira, M., D\u2019Ambrosio, C., Stigliani, A.L., Giorio, G., Misawa, N., and Fraser, P.D. (2019). The road to astaxanthin production in tomato fruit reveals plastid and metabolic adaptation resulting in an unintended high lycopene genotype with delayed over-ripening properties. Plant Biotechnol. J., 1\u201313.","DOI":"10.1111\/pbi.13073"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"81","DOI":"10.5511\/plantbiotechnology.26.81","article-title":"Simple functional analysis of key genes involved in astaxanthin biosynthesis using Arabidopsis cultured cells","volume":"26","author":"Harada","year":"2009","journal-title":"Plant Biotechnol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1104\/pp.16.01297","article-title":"The formation and sequestration of nonendogenous ketocarotenoids in transgenic Nicotiana glauca","volume":"173","author":"Mortimer","year":"2017","journal-title":"Plant Physiol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s11705-017-1628-0","article-title":"Engineering of \u03b2-carotene hydroxylase and ketolase for astaxanthin overproduction in Saccharomyces cerevisiae","volume":"11","author":"Wang","year":"2017","journal-title":"Front. Chem. Sci. Eng."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"840","DOI":"10.3109\/07388551.2015.1049934","article-title":"Molecular farming on rescue of pharma industry for next generations","volume":"36","author":"Moustafa","year":"2016","journal-title":"Crit. Rev. Biotechnol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"e1800050","DOI":"10.1002\/biot.201800050","article-title":"Low protease content in Medicago truncatula cell cultures facilitates recombinant protein production","volume":"13","author":"Santos","year":"2018","journal-title":"Biotechnol. J."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.plantsci.2010.03.009","article-title":"Travel advice on the road to carotenoids in plants","volume":"179","author":"Sanahuja","year":"2010","journal-title":"Plant Sci."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) (2010). Scientific Opinion on the re-evaluation of canthaxanthin (E 161 g) as a food additive. EFSA J., 8, 1852.","DOI":"10.2903\/j.efsa.2010.1852"},{"key":"ref_110","first-page":"85","article-title":"Biosynthesis of Carotenoids and Apocarotenoids by Microorganisms and their Industrial Potential","volume":"Volume 5","author":"Zepka","year":"2018","journal-title":"Progress in Carotenoid Research"}],"container-title":["Plants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2223-7747\/9\/8\/1039\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:01:30Z","timestamp":1760176890000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2223-7747\/9\/8\/1039"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,15]]},"references-count":110,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["plants9081039"],"URL":"https:\/\/doi.org\/10.3390\/plants9081039","relation":{},"ISSN":["2223-7747"],"issn-type":[{"value":"2223-7747","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,15]]}}}