{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T13:01:55Z","timestamp":1790600515287,"version":"4.1.0"},"reference-count":80,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Plant Biotechnology Journal"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The plant\u2010derived specialized metabolite montbretin A (MbA) is under development as an improved treatment for Type 2 diabetes, a worldwide epidemic. MbA is an acylated flavonol glycoside so far only found in small amounts in montbretia (\n                    <jats:italic>Crocosmia<\/jats:italic>\n                    \u00d7\n                    <jats:italic>crocosmiiflora<\/jats:italic>\n                    ) corms. The compound's structural complexity and low natural abundance present major challenges for large\u2010scale production. To enable the development of a scalable MbA production system, we have previously engineered\n                    <jats:italic>Nicotiana benthamiana<\/jats:italic>\n                    to produce MbA. In addition to low levels of MbA,\n                    <jats:italic>N. benthamiana<\/jats:italic>\n                    also produces the pharmaceutically inactive analogues montbretin B and montbretin C, differing from MbA only in their acyl moieties. Follow\u2010up research focusing on precursor engineering has improved MbA yield, but further yield optimization is required to establish\n                    <jats:italic>N. benthamiana<\/jats:italic>\n                    as a scalable MbA production system. Here, we report evidence that transport likely constrains heterologous montbretin production in\n                    <jats:italic>N. benthamiana<\/jats:italic>\n                    and that transporters can be leveraged as bioengineering tools to enhance yield. Specifically, co\u2010expression of tonoplast localized CcABCC4 transporters with montbretin biosynthetic genes in\n                    <jats:italic>N. benthamiana<\/jats:italic>\n                    increased montbretin levels, including those of MbA. Yield increase is likely due to vacuolar sequestration and relies on the presence of an acyl group on the molecule. Eight out of fifteen ABCC4\/14 transporters from plant species not known to produce montbretins also enhanced montbretin accumulation in\n                    <jats:italic>N. benthamiana<\/jats:italic>\n                    . These observations suggest that ABCC transporters might be versatile tools for bioengineering.\n                  <\/jats:p>","DOI":"10.1111\/pbi.70765","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T12:48:28Z","timestamp":1790599708000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tonoplast\u2010Localized\n                    <scp>ABCC<\/scp>\n                    Transporters Enhance Heterologous Production of the Antidiabetic Montbretin A and Its Analogues in\n                    <i>Nicotiana benthamiana<\/i>"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0147-2491","authenticated-orcid":false,"given":"Charlotte","family":"Hijmans","sequence":"first","affiliation":[{"name":"Plant Sciences and Natural Products, Institute of Biology Leiden University  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4742-0654","authenticated-orcid":false,"given":"Filipe Cabrita","family":"Cruz","sequence":"additional","affiliation":[{"name":"Plant Sciences and Natural Products, Institute of Biology Leiden University  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0449-092X","authenticated-orcid":false,"given":"Lars H.","family":"Kruse","sequence":"additional","affiliation":[{"name":"Michael Smith Laboratories University of British Columbia  Vancouver British Columbia Canada"},{"name":"Department of Biology Concordia University  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3637-7956","authenticated-orcid":false,"given":"Joerg","family":"Bohlmann","sequence":"additional","affiliation":[{"name":"Michael Smith Laboratories University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1821-4934","authenticated-orcid":false,"given":"Sandra","family":"Irmisch","sequence":"additional","affiliation":[{"name":"Plant Sciences and Natural Products, Institute of Biology Leiden University  Leiden the 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