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MbA is a complex acylated flavonoid glycoside produced in small amounts in below\u2010ground organs of the perennial plant Montbretia (<jats:italic>Crocosmia<\/jats:italic>\u2009\u00d7\u2009<jats:italic>crocosmiiflora<\/jats:italic>). The lack of a scalable production system limits the development and potential application of MbA as a pharmaceutical or nutraceutical. Previous efforts to reconstruct montbretin biosynthesis in <jats:italic>Nicotiana benthamiana<\/jats:italic> (Nb) resulted in low yields of MbA and higher levels of montbretin B (MbB) and montbretin C (MbC). MbA, MbB, and MbC are nearly identical metabolites differing only in their acyl moieties, derived from caffeoyl\u2010CoA, coumaroyl\u2010CoA, and feruloyl\u2010CoA, respectively. In contrast to MbA, MbB and MbC are not pharmaceutically active. To utilize the montbretia caffeoyl\u2010CoA biosynthesis for improved MbA engineering in Nb, we cloned and characterized enzymes of the shikimate shunt of the general phenylpropanoid pathway, specifically hydroxycinnamoyl\u2010CoA: shikimate hydroxycinnamoyl transferase (CcHCT), <jats:italic>p<\/jats:italic>\u2010coumaroylshikimate 3\u2032\u2010hydroxylase (CcC3\u2032H), and caffeoylshikimate esterase (CcCSE). Gene expression patterns suggest that CcCSE enables the predominant formation of MbA, relative to MbB and MbC, in montbretia. This observation is supported by results from <jats:italic>in vitro<\/jats:italic> characterization of CcCSE and reconstruction of the shikimate shunt in yeast. Using CcHCT together with montbretin biosynthetic genes in multigene constructs resulted in a 30\u2010fold increase of MbA in Nb. This work advances our understanding of the phenylpropanoid pathway and features a critical step towards improved MbA production in bioengineered Nb.<\/jats:p>","DOI":"10.1111\/tpj.16528","type":"journal-article","created":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T08:01:27Z","timestamp":1699948887000},"page":"766-785","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Improved production of the antidiabetic metabolite montbretin A in <i>Nicotiana benthamiana<\/i>: discovery, characterization, and use of <i>Crocosmia<\/i> shikimate shunt genes"],"prefix":"10.1111","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0449-092X","authenticated-orcid":false,"given":"Lars H.","family":"Kruse","sequence":"first","affiliation":[{"name":"Michael Smith Laboratories University of British Columbia  Vancouver British Columbia V6T 1Z4 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick G.","family":"Sunstrum","sequence":"additional","affiliation":[{"name":"Michael Smith Laboratories University of British Columbia  Vancouver British Columbia V6T 1Z4 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Garcia","sequence":"additional","affiliation":[{"name":"Michael Smith Laboratories University of British Columbia  Vancouver British Columbia V6T 1Z4 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo","family":"L\u00f3pez P\u00e9rez","sequence":"additional","affiliation":[{"name":"Michael Smith Laboratories University of British Columbia  Vancouver British Columbia V6T 1Z4 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3146-898X","authenticated-orcid":false,"given":"Sharon","family":"Jancsik","sequence":"additional","affiliation":[{"name":"Michael Smith Laboratories University of British Columbia  Vancouver British Columbia V6T 1Z4 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 V6T 1Z4 Canada"},{"name":"Department of Botany University of British Columbia  Vancouver British Columbia V6T 1Z4 Canada"},{"name":"Department of Forest and Conservation Science University of British Columbia  Vancouver British Columbia V6T 1Z4 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":"Michael Smith Laboratories University of British Columbia  Vancouver British Columbia V6T 1Z4 Canada"},{"name":"Plant Sciences, Institute of Biology Leiden University  Leiden 2333 BE Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/tpj.14373"},{"key":"e_1_2_10_3_1","unstructured":"Andersen R. 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