{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T17:28:07Z","timestamp":1775582887371,"version":"3.50.1"},"reference-count":37,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2019,12,16]],"date-time":"2019-12-16T00:00:00Z","timestamp":1576454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004195","name":"Ocean University of China","doi-asserted-by":"publisher","award":["2018YFD0901005"],"award-info":[{"award-number":["2018YFD0901005"]}],"id":[{"id":"10.13039\/501100004195","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004195","name":"Ocean University of China","doi-asserted-by":"publisher","award":["2018GHY115012"],"award-info":[{"award-number":["2018GHY115012"]}],"id":[{"id":"10.13039\/501100004195","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004195","name":"Ocean University of China","doi-asserted-by":"publisher","award":["ZR2019MC014"],"award-info":[{"award-number":["ZR2019MC014"]}],"id":[{"id":"10.13039\/501100004195","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Siderophores are iron chelators with low molecular weight secreted by microorganisms. Siderophores have the potential to become natural iron fortifiers. To explore the feasibility of the application of Synechococcus sp. PCC7002-derived siderophores as iron fortifiers, Synechococcus sp. PCC7002, as a carrier, was fermented to produce siderophores. The absorption mechanism and anemia intervention effect of siderophores-chelated iron (SCI) were studied through the polarized Caco-2 Cell monolayers and the rat model of iron-deficiency anemia, respectively. The results indicated that siderophores (from Synechococcus sp. PCC7002) had an enhancing effect on iron absorption in polarized Caco-2 cell monolayers. The main absorption site of SCI was duodenum with pH 5.5, and the absorption methods included endocytosis and DMT1, with endocytosis being dominant. The effect of sodium phytate on SCI was less than that of ferrous sulfate. Therefore, SCI could resist inhibitory iron absorption factors in polarized Caco-2 cell monolayers. SCI showed significantly higher relative bioavailability (133.58 \u00b1 15.42%) than ferrous sulfate (100 \u00b1 14.84%) and ferric citrate (66.34 \u00b1 8.715%) in the rat model. Food intake, hemoglobin concentration, and hematocrit and serum iron concentration of rats improved significantly after Fe-repletion. Overall, this study indicated that siderophores derived from Synechococcus sp. PCC7002 could be an effective and feasible iron nutritive fortifier.<\/jats:p>","DOI":"10.3390\/md17120709","type":"journal-article","created":{"date-parts":[[2019,12,17]],"date-time":"2019-12-17T02:59:01Z","timestamp":1576551541000},"page":"709","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Siderophore (from Synechococcus sp. PCC 7002)-Chelated Iron Promotes Iron Uptake in Caco-2 Cells and Ameliorates Iron Deficiency in Rats"],"prefix":"10.3390","volume":"17","author":[{"given":"Xue","family":"Feng","sequence":"first","affiliation":[{"name":"College of Food Science and Engineering, Ocean University of China, Qingdao, Shandong 266003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suisui","family":"Jiang","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering, Ocean University of China, Qingdao, Shandong 266003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fan","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering, Ocean University of China, Qingdao, Shandong 266003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Runfang","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering, Ocean University of China, Qingdao, Shandong 266003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8226-4322","authenticated-orcid":false,"given":"Yuanhui","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering, Ocean University of China, Qingdao, Shandong 266003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingyong","family":"Zeng","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering, Ocean University of China, Qingdao, Shandong 266003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/j.jnutbio.2014.12.006","article-title":"Bioavailability of iron from plant and animal ferritins","volume":"26","author":"Lv","year":"2015","journal-title":"J. Nutr. Biochem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1182\/blood-2018-05-815944","article-title":"Iron deficiency","volume":"133","author":"Camaschella","year":"2019","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"808","DOI":"10.3390\/biom5020808","article-title":"Oxidative stress and the homeodynamics of iron metabolism","volume":"5","author":"Bresgen","year":"2015","journal-title":"Biomolecules"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1146\/annurev-nutr-071812-161205","article-title":"Iron Nutrition and Premenopausal Women: Effects of Poor Iron Status on Physical and Neuropsychological Performance","volume":"Volume 33","author":"Cousins","year":"2013","journal-title":"Annual Review of Nutrition"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1182\/blood-2013-06-508325","article-title":"A systematic analysis of global anemia burden from 1990 to 2010","volume":"123","author":"Kassebaum","year":"2014","journal-title":"Blood"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"nzy004","DOI":"10.1093\/cdn\/nzy004","article-title":"Iron Absorption from Iron-Enriched Aspergillus oryzae Is Similar to Ferrous Sulfate in Healthy Female Subjects","volume":"2","author":"Reddy","year":"2018","journal-title":"Curr. Dev. Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1080\/01904160009382164","article-title":"Production of aerobactin by microorganisms from a compost enrichment culture and soybean utilization","volume":"23","author":"Chen","year":"2000","journal-title":"J. Plant Nutr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"8632","DOI":"10.1021\/jf5018719","article-title":"Enhancement of Non-heme Iron Absorption by Anchovy (Engraulis japonicus) Muscle Protein Hydrolysate Involves a Nanoparticle-Mediated Mechanism","volume":"62","author":"Wu","year":"2014","journal-title":"J. Agric. Food Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/j.bbagen.2010.01.009","article-title":"Phytoferritin and its implications for human health and nutrition","volume":"1800","author":"Zhao","year":"2010","journal-title":"Biochim. Biophys. Acta-Gen. Subj."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.ccr.2009.09.010","article-title":"Iron (III)-siderophore coordination chemistry: Reactivity of marine siderophores","volume":"254","author":"Butler","year":"2010","journal-title":"Coord. Chem. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1146\/annurev.bi.50.070181.003435","article-title":"Microbial iron compounds","volume":"50","author":"Neilands","year":"1981","journal-title":"Annu. Rev. Biochem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1007\/s10534-009-9237-0","article-title":"Siderophores of Marinobacter aquaeolei: Petrobactin and its sulfonated derivatives","volume":"22","author":"Homann","year":"2009","journal-title":"Biometals"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4580","DOI":"10.1021\/cr9002787","article-title":"Microbial Iron Acquisition: Marine and Terrestrial Siderophores","volume":"109","author":"Sandy","year":"2009","journal-title":"Chem. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.4319\/lo.2005.50.6.1918","article-title":"Structure of synechobactins, new siderophores of the marine cyanobacterium Synechococcus sp. PCC 7002","volume":"50","author":"Ito","year":"2005","journal-title":"Limnol. Oceanogr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3754","DOI":"10.1073\/pnas.0637444100","article-title":"Structure and membrane affinity of a suite of amphiphilic siderophores produced by a marine bacterium","volume":"100","author":"Martinez","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5277","DOI":"10.1182\/blood-2008-12-195651","article-title":"Regulation of iron homeostasis in anemia of chronic disease and iron deficiency anemia: Diagnostic and therapeutic implications","volume":"113","author":"Theurl","year":"2009","journal-title":"Blood"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1461S","DOI":"10.3945\/ajcn.2010.28674F","article-title":"Iron bioavailability and dietary reference values","volume":"91","author":"Hurrell","year":"2010","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1023\/A:1015827908309","article-title":"Upper Gastrointestinal (GI) pH in Young, Healthy Men and Women","volume":"7","author":"Dressman","year":"1990","journal-title":"Pharm. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.jtemb.2012.03.015","article-title":"Intestinal iron absorption","volume":"26","author":"Fuqua","year":"2012","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.jff.2019.06.005","article-title":"Dietary gelatin enhances non-heme iron absorption possibly via regulation of systemic iron homeostasis in rats","volume":"59","author":"Wu","year":"2019","journal-title":"J. Funct. Foods"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1007\/s00394-008-0741-8","article-title":"Ascorbic acid uptake affects ferritin, Dcytb and Nramp2 expression in Caco-2 cells","volume":"47","author":"Scheers","year":"2008","journal-title":"Eur. J. Nutr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1024\/0300-9831\/a000029","article-title":"Intestinal Iron Absorption: Regulation by Dietary a Systemic Factors","volume":"80","author":"Sharp","year":"2010","journal-title":"Int. J. Vitam. Nutr. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.beha.2004.08.022","article-title":"Diagnosis and management of iron-deficiency anaemia","volume":"18","author":"Cook","year":"2005","journal-title":"Best Pract. Res. Clin. Haematol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"806S","DOI":"10.1093\/jn\/132.4.806S","article-title":"Fortification: Overcoming technical and practical barriers","volume":"132","author":"Hurrell","year":"2002","journal-title":"J. Nutr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1093\/nutrit\/nuw055","article-title":"Dietary strategies for improving iron status: Balancing safety and efficacy","volume":"75","author":"Prentice","year":"2017","journal-title":"Nutr. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2162","DOI":"10.3945\/jn.110.127209","article-title":"Utilization of Iron from an Animal-Based Iron Source Is Greater Than That of Ferrous Sulfate in Pregnant and Nonpregnant Women","volume":"140","author":"Young","year":"2010","journal-title":"J. Nutr."},{"key":"ref_27","first-page":"R380","article-title":"Effect of exposure to low temperature on normal and iron-deficient subjects","volume":"246","author":"Cubeddu","year":"1984","journal-title":"Am. J. Phys."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.15252\/embr.201540558","article-title":"The Iron age of host-microbe interactions","volume":"16","author":"Soares","year":"2015","journal-title":"EMBO Rep."},{"key":"ref_29","unstructured":"Hoffbrand, V., and Moss, P.A.H. (2015). Hoffbrand\u2019s Essential Haematology, John Wiley & Sons Inc."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.ejogrb.2017.01.003","article-title":"Amino acid chelated iron versus an iron salt in the treatment of iron deficiency anemia with pregnancy: A randomized controlled study","volume":"210","author":"Moety","year":"2017","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1146\/annurev-animal-031412-103717","article-title":"Phytase, a New Life for an \u201cOld\u201d Enzyme","volume":"1","author":"Lei","year":"2013","journal-title":"Annu. Rev. Anim. Biosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/0304-4203(95)00036-Q","article-title":"Physiological-Changes in the Coastal Marine Cyanobacterium Synechococcus sp PCC 7002 Exposed to Low Ferric Ion Levels","volume":"50","author":"Trick","year":"1995","journal-title":"Mar. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1093\/jn\/138.4.659","article-title":"Caco-2 intestinal epithelial cells absorb soybean ferritin by mu(2) (AP2)-dependent endocytosis","volume":"138","author":"Martin","year":"2008","journal-title":"J. Nutr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1006\/abio.1996.0032","article-title":"A fluorescence assay for assessing chelation of intracellular iron in a membrane model system and in mammalian cells","volume":"233","author":"Cabantchik","year":"1996","journal-title":"Anal. Biochem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5705","DOI":"10.1021\/bi300752r","article-title":"Mechanisms of Mammalian Iron Homeostasis","volume":"51","author":"Pantopoulos","year":"2012","journal-title":"Biochemistry"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.jnutbio.2008.04.003","article-title":"Receptor-mediated uptake of ferritin-bound iron by human intestinal Caco-2 cells","volume":"20","author":"Kalgaonkar","year":"2009","journal-title":"J. Nutr. Biochem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1038\/nnano.2010.79","article-title":"Iron from nanocompounds containing iron and zinc is highly bioavailable in rats without tissue accumulation","volume":"5","author":"Hilty","year":"2010","journal-title":"Nat. Nanotechnol."}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/17\/12\/709\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:42:44Z","timestamp":1760190164000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/17\/12\/709"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,16]]},"references-count":37,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["md17120709"],"URL":"https:\/\/doi.org\/10.3390\/md17120709","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,16]]}}}