{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:58:38Z","timestamp":1790776718652,"version":"4.1.0"},"reference-count":38,"publisher":"American Chemical Society (ACS)","issue":"38","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100003443","name":"Ministry of Education and Science of the Russian Federation","doi-asserted-by":"publisher","award":["075-15-2025-527"],"award-info":[{"award-number":["075-15-2025-527"]}],"id":[{"id":"10.13039\/501100003443","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Astaxanthin is a high-value carotenoid used in nutrition, cosmetics, pharmaceuticals, and biotechnology, but its poor water dispersibility and oxidative stability limit its formulation. Here, we engineered yeast Yarrowia lipolytica for the efficient production of glycosylated astaxanthin. Introducing zeaxanthin glucosyltransferase CrtX from Pantoea ananatis into an astaxanthin-producing strain enabled the synthesis of astaxanthin glucosides, confirmed by HR-ESI-MS, 1H NMR, and 2D NMR. Engineering UDP-glucose metabolism by reducing competing pathways and enhancing UDP-glucose biosynthesis improved the astaxanthin glucoside production. The best strategy comprised inactivation of the glycogen synthase gene GSY1 combined with multicopy integration of PGM1 (phosphoglucomutase) and UGP1 (UDP-glucose pyrophosphorylase), achieving 17.6 mg\/L of astaxanthin monoglucoside and 25.1 mg\/L of diglucoside in test-tube cultures. Fed-batch fermentation with glucose yielded 141.6 mg\/L of astaxanthin monoglucoside. When corn syrup was used as a low-cost, sustainable carbon source, the production shifted toward astaxanthin diglucoside, reaching 134.3 mg\/L. These results represent the highest glycosylated astaxanthin titers reported to date.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c01673","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T06:01:50Z","timestamp":1789538510000},"page":"30198-30207","source":"Crossref","is-referenced-by-count":0,"title":["Metabolic Engineering\nof\n                    <i>Yarrowia lipolytica<\/i>\n                    for Efficient\nDe Novo Synthesis of Astaxanthin Glucosides via Enhanced\nUDP-Glucose Supply"],"prefix":"10.1021","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8662-3035","authenticated-orcid":true,"given":"Maria O.","family":"Taratynova","sequence":"first","affiliation":[{"name":"NRC Kurchatov Institute , , Sq. Academician Kurchatova, 1 , ,","place":["Moscow, Russia, 123182"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan M.","family":"Tarasov","sequence":"additional","affiliation":[{"name":"NRC Kurchatov Institute , , Sq. Academician Kurchatova, 1 , ,","place":["Moscow, Russia, 123182"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iuliia M.","family":"Fedyaeva","sequence":"additional","affiliation":[{"name":"NRC Kurchatov Institute , , Sq. Academician Kurchatova, 1 , ,","place":["Moscow, Russia, 123182"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry A.","family":"Dementev","sequence":"additional","affiliation":[{"name":"NRC Kurchatov Institute , , Sq. Academician Kurchatova, 1 , ,","place":["Moscow, Russia, 123182"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrei Kenneth","family":"Whaley","sequence":"additional","affiliation":[{"name":"BioMediCan Inc. , 40471 Encyclopedia Circle , , ,","place":["Fremont, California, United States, 94538"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander S.","family":"Fedorov","sequence":"additional","affiliation":[{"name":"NRC Kurchatov Institute , , Sq. Academician Kurchatova, 1 , ,","place":["Moscow, Russia, 123182"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine","family":"Tran","sequence":"additional","affiliation":[{"name":"BioMediCan Inc. , 40471 Encyclopedia Circle , , ,","place":["Fremont, California, United States, 94538"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tigran V.","family":"Yuzbashev","sequence":"additional","affiliation":[{"name":"Rothamsted Research , , West Common , ,","place":["Harpenden, United Kingdom, AL5 2JQ"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey P.","family":"Sineoky","sequence":"additional","affiliation":[{"name":"NRC Kurchatov Institute , , Sq. Academician Kurchatova, 1 , ,","place":["Moscow, Russia, 123182"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4358-4205","authenticated-orcid":true,"given":"Evgeniya Y.","family":"Yuzbasheva","sequence":"additional","affiliation":[{"name":"BioMediCan Inc. , 40471 Encyclopedia Circle , , ,","place":["Fremont, California, United States, 94538"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"issue":"2","key":"2026093009070126300_cit1","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1080\/10408690590957188","article-title":"Astaxanthin:\nA Review of Its Chemistry and Applications","volume":"46","author":"Higuera-Ciapara","year":"2006","journal-title":"Crit. Rev. Food Sci. Nutr."},{"issue":"4","key":"2026093009070126300_cit2","doi-asserted-by":"publisher","first-page":"300","DOI":"10.3892\/mmr.2022.12816","article-title":"Biological and Neurological Activities of Astaxanthin","volume":"26","author":"Si","year":"2022","journal-title":"Mol. Med. Rep."},{"issue":"4","key":"2026093009070126300_cit3","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1007\/s13749-013-0051-5","article-title":"Synthetic\nAstaxanthin Is Significantly\nInferior to Algal-Based Astaxanthin as an Antioxidant and May Not\nBe Suitable as a Human Nutraceutical Supplement","volume":"12","author":"Capelli","year":"2013","journal-title":"Nutrafoods"},{"issue":"1","key":"2026093009070126300_cit4","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1186\/s40643-021-00415-0","article-title":"High-Level de Novo\nBiosynthesis of Glycosylated Zeaxanthin and Astaxanthin in Escherichia\ncoli","volume":"8","author":"Chen","year":"2021","journal-title":"Bioresour. Bioprocess."},{"issue":"5","key":"2026093009070126300_cit5","doi-asserted-by":"publisher","first-page":"980","DOI":"10.1046\/j.1444-2906.2000.00155.x","article-title":"Antioxidant\nActivity of Polar Carotenoids Including Astaxanthin-Beta-Glucoside\nfrom Marine Bacterium on PC Liposomes","volume":"66","author":"Matsushita","year":"2000","journal-title":"Fish.\nSci."},{"issue":"3","key":"2026093009070126300_cit6","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1016\/S0014-5793(00)02149-9","article-title":"Quenching\nof Singlet Oxygen by Carotenoids Produced in Escherichia coli \u2013\nAttenuation of Singlet Oxygen-mediated Bacterial Killing by Carotenoids","volume":"484","author":"Tatsuzawa","year":"2000","journal-title":"FEBS Lett."},{"issue":"1","key":"2026093009070126300_cit7","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.synbio.2017.12.001","article-title":"Simple Glycolipids of Microbes: Chemistry,\nBiological\nActivity and Metabolic Engineering","volume":"3","author":"Abdel-Mawgoud","year":"2018","journal-title":"Synth. Syst.\nBiotechnol."},{"key":"2026093009070126300_cit8","doi-asserted-by":"publisher","first-page":"121367","DOI":"10.1016\/j.molliq.2023.121367","article-title":"The Effect of Solvent on the Optical\nProperties of Myxoxanthophyll from Synechocystis Sp. PCC6803","volume":"375","author":"Z\u0307bik","year":"2023","journal-title":"J. Mol. Liq."},{"issue":"12","key":"2026093009070126300_cit9","doi-asserted-by":"publisher","first-page":"8141","DOI":"10.1128\/AEM.71.12.8141-8146.2005","article-title":"Diversity of Carotenoid\nSynthesis Gene Clusters from Environmental Enterobacteriaceae Strains","volume":"71","author":"Sedkova","year":"2005","journal-title":"Appl. Environ. Microbiol."},{"issue":"7","key":"2026093009070126300_cit10","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1038\/ja.2009.50","article-title":"Astaxanthin Dirhamnoside,\na New Astaxanthin\nDerivative Produced by a Radio-Tolerant Bacterium, Sphingomonas astaxanthinifaciens","volume":"62","author":"Asker","year":"2009","journal-title":"J. Antibiot."},{"issue":"9","key":"2026093009070126300_cit11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0071946","article-title":"Crocins with High Levels of Sugar\nConjugation Contribute to the Yellow Colours of Early-Spring Flowering\nCrocus Tepals","volume":"8","author":"Rubio Moraga","year":"2013","journal-title":"PLoS One"},{"issue":"1","key":"2026093009070126300_cit12","doi-asserted-by":"publisher","first-page":"8081","DOI":"10.1038\/s41598-024-58700-9","article-title":"Enhancing\nAstaxanthin Biosynthesis\nand Pathway Expansion towards Glycosylated C40 Carotenoids by Corynebacterium\nglutamicum","volume":"14","author":"Go\u0308ttl","year":"2024","journal-title":"Sci. Rep."},{"issue":"8","key":"2026093009070126300_cit13","doi-asserted-by":"publisher","first-page":"2367","DOI":"10.1021\/acs.jafc.1c00350","article-title":"Advanced Strategies for the Synthesis\nof Terpenoids in Yarrowia lipolytica","volume":"69","author":"Li","year":"2021","journal-title":"J. Agric.\nFood Chem."},{"key":"2026093009070126300_cit14","doi-asserted-by":"publisher","DOI":"10.1016\/j.mec.2022.e00213","article-title":"Engineering of Yarrowia lipolytica for Terpenoid Production","volume":"15","author":"Arnesen","year":"2022","journal-title":"Metab. Eng. Commun."},{"issue":"6","key":"2026093009070126300_cit15","doi-asserted-by":"publisher","DOI":"10.1002\/biot.70043","article-title":"A Two-Step\nProcess for Converting\nMethane to Canthaxanthin Using Methylococcus capsulatus (Bath) Biomass\nand Engineered Yarrowia lipolytica","volume":"20","author":"Taratynova","year":"2025","journal-title":"Biotechnol.\nJ."},{"issue":"10","key":"2026093009070126300_cit16","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1016\/j.tibtech.2016.04.010","article-title":"Metabolic Engineering\nfor Expanding the Substrate Range\nof Yarrowia lipolytica","volume":"34","author":"Ledesma-Amaro","year":"2016","journal-title":"Trends Biotechnol."},{"issue":"10","key":"2026093009070126300_cit17","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1002\/yea.2921","article-title":"Yarrowia lipolytica","volume":"29","author":"Nicaud","year":"2012","journal-title":"Yeast"},{"issue":"6","key":"2026093009070126300_cit18","doi-asserted-by":"publisher","first-page":"2943","DOI":"10.1021\/acs.jafc.2c08153","article-title":"Heterologous Expression of the Plant-Derived\nAstaxanthin Biosynthesis\nPathway in Yarrowia lipolytica for Glycosylated Astaxanthin Production","volume":"71","author":"Chen","year":"2023","journal-title":"J. Agric. Food Chem."},{"issue":"1","key":"2026093009070126300_cit19","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1038\/s42003-023-05202-5","article-title":"A DNA Assembly\nToolkit to Unlock\nthe CRISPR\/Cas9 Potential for Metabolic Engineering","volume":"6","author":"Yuzbashev","year":"2023","journal-title":"Commun. Biol."},{"key":"2026093009070126300_cit20","volume-title":"Molecular Cloning: A\nLaboratory Manual","author":"Green","year":"2012","edition":"4"},{"issue":"5","key":"2026093009070126300_cit21","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1038\/nmeth.1318","article-title":"Enzymatic Assembly of DNA Molecules up to Several Hundred\nKilobases","volume":"6","author":"Gibson","year":"2009","journal-title":"Nat. Methods"},{"key":"2026093009070126300_cit22","doi-asserted-by":"publisher","first-page":"101289","DOI":"10.1016\/j.biteb.2022.101289","article-title":"Large-Scale Bioproduction of Natural\nAstaxanthin in Yarrowia lipolytica","volume":"21","author":"Yuzbasheva","year":"2023","journal-title":"Bioresour.\nTechnol. Rep."},{"issue":"6","key":"2026093009070126300_cit23","doi-asserted-by":"publisher","first-page":"1613","DOI":"10.1007\/s00216-009-2837-2","article-title":"Determination of Astaxanthin\nand Astaxanthin Esters\nin the Microalgae Haematococcus pluvialis by LC-(APCI)MS and Characterization\nof Predominant Carotenoid Isomers by NMR Spectroscopy","volume":"395","author":"Holtin","year":"2009","journal-title":"Anal. Bioanal. Chem."},{"issue":"8","key":"2026093009070126300_cit24","doi-asserted-by":"publisher","first-page":"1769","DOI":"10.3390\/molecules25081769","article-title":"Assessment of Astaxanthin\nAccumulation in Hepatocytes of Atlantic Salmon Fed Different Diets\nUsing NMR Spectroscopy","volume":"25","author":"Shumilina","year":"2020","journal-title":"Molecules"},{"issue":"12","key":"2026093009070126300_cit25","doi-asserted-by":"publisher","first-page":"1929","DOI":"10.1021\/np50126a022","article-title":"New Carotenoid Glucosides,\nAstaxanthin\nGlucoside and Adonixanthin Glucoside, Isolated from the Astaxanthin-Producing\nMarine Bacterium, Agrobacterium aurantiacum","volume":"58","author":"Yokoyama","year":"1995","journal-title":"J. Nat. Prod."},{"issue":"2","key":"2026093009070126300_cit26","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1128\/MMBR.00038-05","article-title":"Cell Wall Assembly in Saccharomyces cerevisiae","volume":"70","author":"Lesage","year":"2006","journal-title":"Microbiol. Mol. Biol. Rev."},{"issue":"4","key":"2026093009070126300_cit27","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1016\/j.bbrc.2015.10.090","article-title":"UDP-Glucose Pyrophosphorylase Ugp1 Is Involved in Oxidative\nStress Response and Long-Term Survival during Stationary Phase in\nSaccharomyces cerevisiae","volume":"467","author":"Yi","year":"2015","journal-title":"Biochem. Biophys.\nRes. Commun."},{"issue":"3","key":"2026093009070126300_cit28","doi-asserted-by":"publisher","first-page":"fox020","DOI":"10.1093\/femsyr\/fox020","article-title":"Sugar versus\nFat: Elimination of Glycogen Storage Improves Lipid Accumulation in\nYarrowia lipolytica","volume":"17","author":"Bhutada","year":"2017","journal-title":"FEMS Yeast Res."},{"key":"2026093009070126300_cit29","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1007\/978-3-642-21467-7_2","article-title":"Genetics and Regulation of Glycogen and Trehalose Metabolism in Saccharomyces\ncerevisiae","volume-title":"Microbial Stress Tolerance\nfor Biofuels","author":"Franc\u0327ois","year":"2012"},{"issue":"6","key":"2026093009070126300_cit30","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1111\/j.1574-6976.2010.00220.x","article-title":"Regulation\nof Glycogen Metabolism in Yeast and Bacteria","volume":"34","author":"Wilson","year":"2010","journal-title":"FEMS Microbiol. Rev."},{"key":"2026093009070126300_cit31","doi-asserted-by":"publisher","DOI":"10.1016\/j.btre.2021.e00646","article-title":"Global Transcriptome\nProfiling Reveals Genes Responding\nto Overproduction of a Small Secretory, a High Cysteine- and a High\nGlycosylation-Bearing Protein in Yarrowia lipolytica","volume":"31","author":"Korpys-Woz\u0301niak","year":"2021","journal-title":"Biotechnol. Rep."},{"issue":"1","key":"2026093009070126300_cit32","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1111\/j.1432-1033.1994.tb19996.x","article-title":"Isolation of the ALG5\nLocus Encoding the UDP-Glucose:Dolichyl-Phosphate Glucosyltransferase\nfrom Saccharomyces cerevisiae","volume":"224","author":"Heesen","year":"1994","journal-title":"Eur. J. Biochem."},{"issue":"2","key":"2026093009070126300_cit33","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.synbio.2021.03.002","article-title":"Systematic\nOptimization of the Yeast Cell Factory for Sustainable and High Efficiency\nProduction of Bioactive Ginsenoside Compound K","volume":"6","author":"Wang","year":"2021","journal-title":"Synth. Syst. Biotechnol."},{"issue":"1","key":"2026093009070126300_cit34","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1186\/s12862-015-0515-x","article-title":"Characterizing\nSelective Pressures on the Pathway for de Novo Biosynthesis of Pyrimidines\nin Yeast","volume":"15","author":"Hermansen","year":"2015","journal-title":"BMC Evol. Biol."},{"issue":"4","key":"2026093009070126300_cit35","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1007\/s10059-010-0047-6","article-title":"Structural Basis\nfor the Reaction Mechanism of UDP-Glucose Pyrophosphorylase","volume":"29","author":"Kim","year":"2010","journal-title":"Mol. Cells"},{"issue":"19","key":"2026093009070126300_cit36","doi-asserted-by":"publisher","first-page":"6005","DOI":"10.1111\/febs.16471","article-title":"Regulatory\nPhosphorylation Event\nof Phosphoglucomutase 1 Tunes Its Activity to Regulate Glycogen Metabolism","volume":"289","author":"Doello","year":"2022","journal-title":"FEBS J."},{"key":"2026093009070126300_cit37","doi-asserted-by":"publisher","first-page":"1516522","DOI":"10.3389\/fbioe.2025.1516522","article-title":"Response Surface-Based\nMedia Optimization for Astaxanthin Production in Corynebacterium glutamicum","volume":"13","author":"Meyer","year":"2025","journal-title":"Front. Bioeng. Biotechnol."},{"issue":"4","key":"2026093009070126300_cit38","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1111\/lam.12463","article-title":"Overexpression\nof ZWF1 and POS5 Improves Carotenoid\nBiosynthesis in Recombinant Saccharomyces cerevisiae","volume":"61","author":"Zhao","year":"2015","journal-title":"Lett. Appl. Microbiol."}],"container-title":["Journal of Agricultural\nand Food Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jafc.6c01673","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/38\/30198\/68525789\/acs.jafc.6c01673.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/38\/30198\/68525789\/acs.jafc.6c01673.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:23:09Z","timestamp":1790774589000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jafcau\/article\/74\/38\/30198\/5430901\/Metabolic-Engineering-of-Yarrowia-lipolyticafor"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,16]]},"references-count":38,"journal-issue":{"issue":"38","published-online":{"date-parts":[[2026,9,16]]},"published-print":{"date-parts":[[2026,9,30]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jafc.6c01673","relation":{},"ISSN":["0021-8561","1520-5118"],"issn-type":[{"value":"0021-8561","type":"print"},{"value":"1520-5118","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,16]]}}}