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Bioprocess."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>p<\/jats:italic>\n                    -Coumaric acid (p-CA) is a key aromatic precursor for the biosynthesis of flavonoids, stilbenoids, and other high-value phenylpropanoids. While microbial production of p-CA typically relies on sugar-based substrates, methanol offers a sustainable and cost-effective alternative, though its use for aromatic biosynthesis remains unexplored. Here, we report the first de novo production of p-CA from methanol using engineered methylotrophic yeast\n                    <jats:italic>Pichia pastoris<\/jats:italic>\n                    . Through heterologous expression of a tyrosine ammonia-lyase and implementing a balanced push\u2013pull strategy in the shikimate pathway using feedback-resistant variants of DAHP synthase (\n                    <jats:italic>ARO4<\/jats:italic>\n                    ) and chorismate mutase (\n                    <jats:italic>ARO7<\/jats:italic>\n                    ), carbon flux from methanol-derived C3 and C4 precursors was effectively redirected toward aromatic biosynthesis. Shake-flask studies revealed strong gene-dosage-dependent p-CA production, but strains with high-copy numbers suffered metabolic burden under high-density fermentation. Fed-batch bioreactor cultivation demonstrated that a moderate-copy strain achieved the highest titer of 704 \u00b1 6\u00a0mg\/L, outperforming high-copy variants in robustness and scalability. This study establishes\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>pastoris<\/jats:italic>\n                    as a promising chassis for methanol-based aromatic production and highlights the critical trade-off between pathway amplification and cellular fitness in C1 biomanufacturing.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1186\/s40643-026-01068-7","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T08:53:12Z","timestamp":1778662392000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Methanol-based biosynthesis of p-coumaric acid by engineered Pichia pastoris"],"prefix":"10.1186","volume":"13","author":[{"given":"Mengyuan","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayu","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuxian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoxia","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanping","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaizhi","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3305-1141","authenticated-orcid":false,"given":"Taicheng","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"1068_CR1","doi-asserted-by":"publisher","first-page":"127535","DOI":"10.1016\/j.foodchem.2020.127535","volume":"338","author":"FF Ara\u00fajo","year":"2021","unstructured":"Ara\u00fajo FF, Farias D, Neri-Numa IA, Pastore GM (2021) Polyphenols and their applications: an approach in food chemistry and innovation potential. 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