{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T14:08:21Z","timestamp":1789567701779,"version":"build-2803163510"},"reference-count":63,"publisher":"American Chemical Society (ACS)","issue":"36","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100003787","name":"Natural Science Foundation of Hebei Province","doi-asserted-by":"publisher","award":["C2025110036"],"award-info":[{"award-number":["C2025110036"]}],"id":[{"id":"10.13039\/501100003787","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFF1104004"],"award-info":[{"award-number":["2023YFF1104004"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Central Government Guiding Local Science and Technology Development Funds of Hebei Province","award":["246Z2811G"],"award-info":[{"award-number":["246Z2811G"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Tetrahydrocurcumin, a major hydrogenated curcumin derivative with improved stability and bioavailability, represents a promising ingredient for functional foods and nutraceuticals. Curcumin reductases (CurAs) catalyze the eco-friendly enzymatic conversion of curcumin to tetrahydrocurcumin, yet few CurA homologues have been identified. Here, using two characterized CurAs as seed sequences, we developed a data-driven screening pipeline integrating sequence clustering and structure-based evaluation. Functional characterization of 15 prioritized candidates identified RmCurA from Rhodomicrobium as the top-performing enzyme. It rapidly and fully converts curcumin to tetrahydrocurcumin within 8 min at nanomolar enzyme loading and favors natural demethylated curcuminoids over heavily methylated analogs. Molecular dynamics simulations revealed that RmCurA forms an obligate homodimer with rigid, stable architecture, and its dual energy minima indicative of interconvertible functional conformations supporting high catalytic activity. This work establishes an efficient biocatalytic route toward tetrahydrocurcumin and provides a general framework to discover high-performance enzymes for natural product modification.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c08606","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T16:13:11Z","timestamp":1788451991000},"page":"28594-28608","source":"Crossref","is-referenced-by-count":0,"title":["Structure-Sequence\nGuided Discovery of Highly Efficient\nCurcumin Reductase Enables Biocatalytic Reductive Editing of Curcuminoids"],"prefix":"10.1021","volume":"74","author":[{"given":"Jiabao","family":"Ying","sequence":"first","affiliation":[{"name":"Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences , , ,","place":["Beijing, China, 100193"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences , , ,","place":["Beijing, China, 100193"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4991-639X","authenticated-orcid":true,"given":"Peicheng","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences , , ,","place":["Beijing, China, 100193"]},{"name":"Institute of Food Science Technology Nutrition and Health (Cangzhou), Chinese Academy of Agricultural Sciences , ,","place":["Cangzhou, China, 061001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujun","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences , , ,","place":["Beijing, China, 100193"]},{"name":"Institute of Food Science Technology Nutrition and Health (Cangzhou), Chinese Academy of Agricultural Sciences , ,","place":["Cangzhou, China, 061001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences , , ,","place":["Beijing, China, 100193"]},{"name":"Institute of Food Science Technology Nutrition and Health (Cangzhou), Chinese Academy of Agricultural Sciences , ,","place":["Cangzhou, China, 061001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2063-601X","authenticated-orcid":true,"given":"Jiaoyan","family":"Ren","sequence":"additional","affiliation":[{"name":"South China University of Technology , , ,","place":["Guangzhou, China, 510640"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1937-5174","authenticated-orcid":true,"given":"Yulu","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences , , ,","place":["Beijing, China, 100193"]},{"name":"Institute of Food Science Technology Nutrition and Health (Cangzhou), Chinese Academy of Agricultural Sciences , ,","place":["Cangzhou, China, 061001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4656-7734","authenticated-orcid":true,"given":"Fengjiao","family":"Xin","sequence":"additional","affiliation":[{"name":"Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences , , ,","place":["Beijing, China, 100193"]},{"name":"Institute of Food Science Technology Nutrition and Health (Cangzhou), Chinese Academy of Agricultural Sciences , ,","place":["Cangzhou, China, 061001"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"issue":"2","key":"2026091609085146000_cit1","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1038\/s44160-024-00673-8","article-title":"Multisite modifications of arenes using ketones as\nremovable handles enabled by Pd and norbornene cooperative catalysis","volume":"4","author":"Tao","year":"2025","journal-title":"Nat. Synth."},{"issue":"6","key":"2026091609085146000_cit2","doi-asserted-by":"publisher","first-page":"2267","DOI":"10.1021\/jacsau.4c00206","article-title":"Formal single atom editing of the\nglycosylated natural\nproduct fidaxomicin improves acid stability and retains antibiotic\nactivity","volume":"4","author":"Ferrara","year":"2024","journal-title":"JACS Au"},{"issue":"12","key":"2026091609085146000_cit3","first-page":"651","article-title":"Evaluation\nof anti-inflammatory property\nof curcumin (diferuloyl methane) in patients with postoperative inflammation","volume":"24","author":"Satoskar","year":"1986","journal-title":"Int. J. Clin. Pharmacol., Ther., Toxicol."},{"issue":"4","key":"2026091609085146000_cit4","doi-asserted-by":"publisher","first-page":"1725","DOI":"10.1248\/cpb.33.1725","article-title":"Natural antioxidants.\nIII. Antioxidative components isolated from rhizome of Curcuma longa L","volume":"33","author":"Toda","year":"1985","journal-title":"Chem. Pharm. Bull."},{"issue":"2","key":"2026091609085146000_cit5","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/0304-3835(85)90159-4","article-title":"Potential anticancer\nactivity of turmeric (Curcuma longa)","volume":"29","author":"Kuttan","year":"1985","journal-title":"Cancer Lett."},{"issue":"10","key":"2026091609085146000_cit6","doi-asserted-by":"publisher","first-page":"4297","DOI":"10.1021\/jf990308d","article-title":"Antibacterial\nactivity\nof turmeric oil: a byproduct from curcumin manufacture","volume":"47","author":"Negi","year":"1999","journal-title":"J. Agric. Food Chem."},{"issue":"1","key":"2026091609085146000_cit7","doi-asserted-by":"publisher","first-page":"13","DOI":"10.4103\/0972-2327.40220","article-title":"The effect\nof curcumin (turmeric) on Alzheimer\u2019s\ndisease: An overview","volume":"11","author":"Mishra","year":"2008","journal-title":"Ann. Indian Acad. Neurol."},{"issue":"16","key":"2026091609085146000_cit8","doi-asserted-by":"publisher","first-page":"6615","DOI":"10.1073\/pnas.1016217108","article-title":"Discovery\nof the curcumin metabolic pathway involving a unique enzyme in an\nintestinal microorganism","volume":"108","author":"Hassaninasab","year":"2011","journal-title":"Proc. Natl. Acad.\nSci. U.S.A."},{"issue":"11","key":"2026091609085146000_cit9","doi-asserted-by":"publisher","first-page":"1325","DOI":"10.1111\/bph.13621","article-title":"Curcumin, the golden nutraceutical:\nmultitargeting for multiple chronic diseases","volume":"174","author":"Kunnumakkara","year":"2017","journal-title":"Br. J. Pharmacol."},{"issue":"11","key":"2026091609085146000_cit10","doi-asserted-by":"publisher","DOI":"10.3390\/foods13111774","article-title":"Neuroprotective\neffects of curcumin in neurodegenerative diseases","volume":"13","author":"Genchi","year":"2024","journal-title":"Foods"},{"key":"2026091609085146000_cit11","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1216708","article-title":"Effects of dietary polyphenol curcumin\nsupplementation on metabolic, inflammatory, and oxidative stress indices\nin patients with metabolic syndrome: a systematic review and meta-analysis\nof randomized controlled trials","volume":"14","author":"Qiu","year":"2023","journal-title":"Front. Endocrinol."},{"issue":"1","key":"2026091609085146000_cit12","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1093\/advances\/nmx011","article-title":"The problem\nof curcumin and its bioavailability: could its gastrointestinal influence\ncontribute to its overall health-enhancing effects?","volume":"9","author":"Lopresti","year":"2018","journal-title":"Adv. Nutr."},{"issue":"41","key":"2026091609085146000_cit13","doi-asserted-by":"publisher","first-page":"26266","DOI":"10.1021\/acs.jafc.5c07455","article-title":"Structure-guided evolution of curcumin reductase for sustainable\ntetrahydrocurcumin biosynthesis","volume":"73","author":"Hao","year":"2025","journal-title":"J. Agric. Food\nChem."},{"issue":"4","key":"2026091609085146000_cit14","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1007\/BF01965935","article-title":"Anti-inflammatory\nand irritant activities of curcumin analogues in rats","volume":"12","author":"Mukhopadhyay","year":"1982","journal-title":"Agents Actions"},{"issue":"7","key":"2026091609085146000_cit15","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1080\/08860220701540326","article-title":"Antihyperlipidemic\neffect of curcumin and tetrahydrocurcumin\nin experimental type 2 diabetic rats","volume":"29","author":"Pari","year":"2007","journal-title":"Renal\nFailure"},{"key":"2026091609085146000_cit16","unstructured":"European Commission.\n          .  Commission\nImplementing Regulation (EU) \/961 of 20 June 2022 Authorising the\nPlacing on the Market of Tetrahydrocurcuminoids as a Novel Food and\nAmending Implementing Regulation (EU) 2017\/24702022L165, Official Journal of the European Union202241-45."},{"issue":"23","key":"2026091609085146000_cit17","doi-asserted-by":"publisher","first-page":"10234","DOI":"10.1021\/ie901217r","article-title":"Liquid-phase hydrogenation of crotonaldehyde\nover platinum- and palladium-based catalysts","volume":"48","author":"Campo","year":"2009","journal-title":"Ind. Eng. Chem. Res."},{"issue":"2","key":"2026091609085146000_cit18","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1021\/acs.chemrev.7b00203","article-title":"Role of biocatalysis\nin sustainable chemistry","volume":"118","author":"Sheldon","year":"2018","journal-title":"Chem. 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Comput.-Aided Mol. Des."},{"issue":"W1","key":"2026091609085146000_cit32","doi-asserted-by":"publisher","first-page":"W478","DOI":"10.1093\/nar\/gkaf377","article-title":"ProteinsPlus: a publicly\navailable resource for protein structure\nmining","volume":"53","author":"Ehrt","year":"2025","journal-title":"Nucleic Acids Res."},{"issue":"W1","key":"2026091609085146000_cit33","doi-asserted-by":"publisher","first-page":"W463","DOI":"10.1093\/nar\/gkaf361","article-title":"PLIP 2025:\nintroducing protein-protein interactions to the protein-ligand interaction\nprofiler","volume":"53","author":"Schake","year":"2025","journal-title":"Nucleic Acids Res."},{"issue":"8","key":"2026091609085146000_cit34","doi-asserted-by":"publisher","first-page":"3891","DOI":"10.1021\/acs.jcim.1c00203","article-title":"AutoDock Vina 1.2.0:\nnew docking methods, expanded force field, and Python bindings","volume":"61","author":"Eberhardt","year":"2021","journal-title":"J. Chem. Inf. 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Agric.\nFood Chem."},{"issue":"4","key":"2026091609085146000_cit57","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1002\/pro.3112","article-title":"An\napproach to functionally relevant clustering\nof the protein universe: Active site profile-based clustering of protein\nstructures and sequences","volume":"26","author":"Knutson","year":"2017","journal-title":"Protein Sci."},{"issue":"4","key":"2026091609085146000_cit58","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbaf331","article-title":"Deep learning-enhanced\nclustering and classification of protein molecule tertiary structures\nusing weighted distance matrices","volume":"26","author":"Liu","year":"2025","journal-title":"Briefings\nBioinf."},{"issue":"47","key":"2026091609085146000_cit59","doi-asserted-by":"publisher","first-page":"18431","DOI":"10.1021\/acs.jafc.3c07204","article-title":"Sequence-\nand structure-based mining of thermostable D-allulose 3-epimerase\nand computer-guided protein engineering to improve enzyme activity","volume":"71","author":"Qi","year":"2023","journal-title":"J. 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