{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T10:06:30Z","timestamp":1789725990113,"version":"4.0.1"},"reference-count":47,"publisher":"Wiley","issue":"52","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Confronting the dual crisis of escalating global protein demand and unsustainable agriculture necessitates transformative solutions. Here, we pioneer evolutionary insights from maize nitrogen optimization via asparagine synthetase (ASNS) to rewire metabolism in\n                    <jats:italic>Pichia pastoris<\/jats:italic>\n                    . Empirically, the tri\u2010copy ASNS strain achieved superior protein titers: 62.48% crude protein, 47.86% total amino acids, and 8.05% branched\u2010chain amino acids, nutritionally surpassing conventional protein sources. Genome\u2010scale modeling and transcriptomic studies provided convergent evidence that ASNS overexpression drove global metabolic rewiring through predicted synergistic coupling between aspartate metabolism and the tricarboxylic acid cycle. Mechanistically, ASNS overexpression unlocked a previously uncharacterized nitrogen sensor\u2010regulator circuit by inducing\n                    <jats:italic>PAS_chr1\u20101_0158<\/jats:italic>\n                    , validated in amplifying intracellular nitrogen flux and driving a self\u2010reinforcing cycle of ammonia assimilation. This work validated evolutionary conservation of nitrogen optimization strategies across kingdoms, established the first scalable blueprint for carbon\u2013nitrogen co\u2010optimized microbial cell factories, decouples sustainable SCP production from agricultural constraints, and offers a scalable solution to the global protein crisis.\n                  <\/jats:p>","DOI":"10.1002\/advs.202517703","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T19:31:52Z","timestamp":1782243112000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cross Kingdom Metabolic Engineering Paradigm Elevating Sustainable Protein Production"],"prefix":"10.1002","volume":"13","author":[{"given":"Yuanyuan","family":"Du","sequence":"first","affiliation":[{"name":"State Key Laboratory of Engineering Biology for Low\u2010Carbon Manufacturing Tianjin Institute of Industrial Biotechnology Chinese Academy of Sciences  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changyu","family":"Pi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Engineering Biology for Low\u2010Carbon Manufacturing Tianjin Institute of Industrial Biotechnology Chinese Academy of Sciences  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Hong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Engineering Biology for Low\u2010Carbon Manufacturing Tianjin Institute of Industrial Biotechnology Chinese Academy of Sciences  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Gao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Engineering Biology for Low\u2010Carbon Manufacturing Tianjin Institute of Industrial Biotechnology Chinese Academy of Sciences  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9225-5574","authenticated-orcid":false,"given":"Xin","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Engineering Biology for Low\u2010Carbon Manufacturing Tianjin Institute of Industrial Biotechnology Chinese Academy of Sciences  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/padr.12508"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2319001121"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s42055\u2010023\u201000052\u20109"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00394\u2010024\u201003358\u20102"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2025.04.018"},{"key":"e_1_2_9_7_1","first-page":"1","article-title":"Single Cell Protein: A Resort to Global Protein Challenge and Waste Management","volume":"1","author":"Ukaegbu\u2010Obi K. 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