{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:43:22Z","timestamp":1792784602920,"version":"4.5.0"},"reference-count":39,"publisher":"American Chemical Society (ACS)","issue":"41","license":[{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC3401301"],"award-info":[{"award-number":["2022YFC3401301"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013088","name":"Qinglan Project of Jiangsu Province of China","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100013088","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"},{"id":"https:\/\/ror.org\/01cvdks57","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/na","name":"Special Fund for Centrally-administered Universities to Support the High-quality Development of Jiangsu Province","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Industrial production of Bifidobacterium bifidum (B. bifidum) is constrained by its poor use of conventional nitrogen sources. Previous studies have demonstrated that supplementation with proline-containing peptides (PCPs) enhances both growth density and freeze-drying survival rate of B. bifidum. Thus, we developed an in silico-guided strategy to prepare proline-containing peptide-rich hydrolyzates tailored to its nitrogen preference. Casein, glutenin, and whey protein hydrolyzate were selected as substrates, and six enzymatic hydrolysis routes were designed using simulated digestion and molecular docking. The optimal nitrogen source, WA-CAF, a nitrogen source rich in PCPs, enabled B. bifidum CCFM16 to achieve higher biomass and freeze-drying survival rate than De Man-Rogosa-Sharpe (MRS) medium at a lower dosage. Viable-cell yield per unit nitrogen increased by 178.6%. Peptidomics revealed that efficiently utilized peptides were shorter than 10 residues, enriched in Pro, Leu, and Val, with internal Pro residues. This work provides a practical, sequence-guided nitrogen-source design framework for difficult-to-cultivate probiotics.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c09084","type":"journal-article","created":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T17:01:49Z","timestamp":1791824509000},"page":"32549-32561","source":"Crossref","is-referenced-by-count":0,"title":["In-Silico Rational\nDesign of Proline-Containing Peptides\n(PCPs) for Efficient Utilization by\n                    <i>Bifidobacterium bifidum<\/i>\n                    and Identification of Their Key Transported\nSequences"],"prefix":"10.1021","volume":"74","author":[{"given":"Xin","family":"Qian","sequence":"first","affiliation":[{"name":"Jiangnan University , , ,","place":["Wuxi, China, 214122"]},{"name":"Jiangnan University , , ,","place":["Wuxi, China, 214122"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6342-1254","authenticated-orcid":true,"given":"Bingyong","family":"Mao","sequence":"additional","affiliation":[{"name":"Jiangnan University , , ,","place":["Wuxi, China, 214122"]},{"name":"Jiangnan University , , ,","place":["Wuxi, China, 214122"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9663-3974","authenticated-orcid":true,"given":"Fei","family":"Liu","sequence":"additional","affiliation":[{"name":"Jiangnan University , , ,","place":["Wuxi, China, 214122"]},{"name":"Jiangnan University , , ,","place":["Wuxi, China, 214122"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6391-3075","authenticated-orcid":true,"given":"Xin","family":"Tang","sequence":"additional","affiliation":[{"name":"Jiangnan University , , ,","place":["Wuxi, China, 214122"]},{"name":"Jiangnan University , , ,","place":["Wuxi, China, 214122"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5896-6487","authenticated-orcid":true,"given":"Hongtao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Jiangnan University , , , ,","place":["Wuxi, China, 214122"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuxiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Jiangnan University , , ,","place":["Wuxi, China, 214122"]},{"name":"Jiangnan University , , ,","place":["Wuxi, China, 214122"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0605-2675","authenticated-orcid":true,"given":"Qixiao","family":"Zhai","sequence":"additional","affiliation":[{"name":"Jiangnan University , , ,","place":["Wuxi, China, 214122"]},{"name":"Jiangnan University , , ,","place":["Wuxi, China, 214122"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4516-0799","authenticated-orcid":true,"given":"Jianxin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Jiangnan University , , ,","place":["Wuxi, China, 214122"]},{"name":"Jiangnan University , , ,","place":["Wuxi, China, 214122"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3348-4710","authenticated-orcid":true,"given":"Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Jiangnan University , , ,","place":["Wuxi, China, 214122"]},{"name":"Jiangnan University , , ,","place":["Wuxi, China, 214122"]},{"name":"Jiangnan University , , ,","place":["Wuxi, China, 214122"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3559-2332","authenticated-orcid":true,"given":"Shumao","family":"Cui","sequence":"additional","affiliation":[{"name":"Jiangnan University , , ,","place":["Wuxi, China, 214122"]},{"name":"Jiangnan University , , ,","place":["Wuxi, China, 214122"]},{"name":"Jiangnan University , , ,","place":["Wuxi, China, 214122"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,10,12]]},"reference":[{"key":"2026102109081478700_cit1","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.3389\/fmicb.2016.01204","article-title":"Gut Bifidobacteria populations in human health and aging","volume":"7","author":"Arboleya","year":"2016","journal-title":"Front.\nMicrobiol."},{"key":"2026102109081478700_cit2","doi-asserted-by":"publisher","first-page":"437","DOI":"10.3389\/fmicb.2014.00437","article-title":"Bifidobacterium bifidum as an example of a specialized human gut commensal","volume":"5","author":"Turroni","year":"2014","journal-title":"Front. 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Appl.\nMicrobiol."},{"issue":"22","key":"2026102109081478700_cit6","first-page":"335","article-title":"Enhancement\nof Innate Immune Function in Mice by Bifidobacterium bifidum FL-228.1","volume":"44","author":"Yu","year":"2023","journal-title":"Sci. Technol. Food Ind."},{"issue":"1","key":"2026102109081478700_cit7","doi-asserted-by":"publisher","first-page":"18222","DOI":"10.1038\/s41598-019-54696-9","article-title":"Deciphering the metabolic\ncapabilities of Bifidobacteria using genome-scale\nmetabolic models","volume":"9","author":"Devika","year":"2019","journal-title":"Sci. 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Rep."},{"key":"2026102109081478700_cit19","doi-asserted-by":"publisher","first-page":"103611","DOI":"10.1016\/j.fbio.2024.103611","article-title":"Mechanism analysis\nof methionine\ninhibiting growth of Bifidobacterium bifidum","volume":"57","author":"Gu","year":"2024","journal-title":"Food Biosci."},{"issue":"22","key":"2026102109081478700_cit20","doi-asserted-by":"publisher","first-page":"4401","DOI":"10.1080\/10408398.2024.2387328","article-title":"The growth-promoting effects of protein hydrolysates and their derived\npeptides on probiotics: structure-activity relationships, mechanisms\nand future perspectives","volume":"65","author":"Huang","year":"2025","journal-title":"Crit. Rev. 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Chem."},{"issue":"2","key":"2026102109081478700_cit24","first-page":"255","article-title":"Determination\nand\nanalysis of 17 amino acids in ginseng from different origins in modern\nfood","volume":"42","author":"Huang","year":"2021","journal-title":"Food Sci."},{"key":"2026102109081478700_cit25","first-page":"192","article-title":"Study on molecular\nweight distribution of small molecular\npeptides in special dietary foods by gel chromatography (GPC)","volume":"17","author":"Huang","year":"2021","journal-title":"Modern Food"},{"issue":"1","key":"2026102109081478700_cit26","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1007\/s11947-024-03512-y","article-title":"Effects of Cross Stress on the Survival\nof Lactiplantibacillus plantarum LIP-1 After Freeze-Drying","volume":"18","author":"Yijian","year":"2025","journal-title":"Food Bioprocess Technol."},{"issue":"7","key":"2026102109081478700_cit27","doi-asserted-by":"publisher","first-page":"4117","DOI":"10.1128\/AEM.71.7.4117-4120.2005","article-title":"Assessment of soil\nmicrobial community structure by use of taxon-specific quantitative\nPCR assays","volume":"71","author":"Fierer","year":"2005","journal-title":"Appl. Environ. Microbiol."},{"key":"2026102109081478700_cit28","doi-asserted-by":"publisher","first-page":"102059","DOI":"10.1016\/j.fochx.2024.102059","article-title":"Evaluation\nof UHT milk spoilage caused by proteases from psychrophilic bacteria\nbased on peptidomics","volume":"24","author":"Xu","year":"2024","journal-title":"Food Chem."},{"issue":"1","key":"2026102109081478700_cit29","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/s43586-023-00205-2","article-title":"Peptidomics","volume":"3","author":"Hellinger","year":"2023","journal-title":"Nat. Rev. Methods\nPrimers"},{"issue":"2","key":"2026102109081478700_cit30","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1038\/s41564-023-01593-7","article-title":"Ammonia-oxidizing\nbacteria\nand archaea exhibit differential nitrogen source preferences","volume":"9","author":"Qin","year":"2024","journal-title":"Nat. Microbiol."},{"key":"2026102109081478700_cit31","doi-asserted-by":"publisher","first-page":"906","DOI":"10.3389\/fmicb.2019.00906","article-title":"Insights into the complexity\nof yeast extract peptides and their utilization by streptococcus thermophilus","volume":"10","author":"Proust","year":"2019","journal-title":"Front. Microbiol."},{"issue":"21","key":"2026102109081478700_cit32","doi-asserted-by":"publisher","first-page":"8211","DOI":"10.1021\/acs.jafc.3c00603","article-title":"Identification\nof Novel Dipeptidyl Peptidase-IV Inhibitory Peptides in Chickpea Protein\nHydrolysates","volume":"71","author":"Zan","year":"2023","journal-title":"J. Agric. 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Struct.\nMol. Biol."},{"issue":"8","key":"2026102109081478700_cit37","doi-asserted-by":"publisher","first-page":"1682","DOI":"10.1111\/ijfs.12138","article-title":"Bifidobacterial growth\u2013promoting\neffect of yak milk\n\u03ba-casein hydrolysates produced with different proteases","volume":"48","author":"Tang","year":"2013","journal-title":"Int. J. Food Sci. Technol."},{"issue":"2","key":"2026102109081478700_cit38","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.foodchem.2003.09.034","article-title":"Caseinomacropeptide and whey protein\nconcentrate enhance Bifidobacterium lactis growth\nin milk","volume":"86","author":"Janer","year":"2004","journal-title":"Food Chem."},{"issue":"1","key":"2026102109081478700_cit39","doi-asserted-by":"publisher","first-page":"134195","DOI":"10.1016\/j.foodchem.2022.134195","article-title":"Identification and\ncharacterization of soybean peptides and their\nfractions used by Lacticaseibacillus rhamnosus Lra05","volume":"401","author":"Zhang","year":"2023","journal-title":"Food Chem."}],"container-title":["Journal of Agricultural\nand Food Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jafc.6c09084","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/41\/32549\/68824406\/acs.jafc.6c09084.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/41\/32549\/68824406\/acs.jafc.6c09084.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T13:17:22Z","timestamp":1792588642000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jafcau\/article\/74\/41\/32549\/5449233\/In-Silico-Rational-Design-of-Proline-Containing"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,12]]},"references-count":39,"journal-issue":{"issue":"41","published-online":{"date-parts":[[2026,10,12]]},"published-print":{"date-parts":[[2026,10,21]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jafc.6c09084","relation":{},"ISSN":["0021-8561","1520-5118"],"issn-type":[{"value":"0021-8561","type":"print"},{"value":"1520-5118","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,12]]}}}