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Among the most frequently prescribed antihypertensive first\u2010line drugs are synthetic angiotensin I\u2010converting enzyme inhibitors (ACEI). However, since \u00a0their use in hypertension therapy has been linked to various side effects, interest in the application of food\u2010derived ACEI peptides (ACEIp) as antihypertensive agents is rapidly growing. Although promising, the industrial production of ACEIp through conventional methods such as chemical synthesis or enzymatic hydrolysis of food proteins has been\u00a0proven troublesome. We here provide an overview of\u00a0current antihypertensive therapeutics, focusing on ACEI, and illustrate how biotechnology and bioengineering can overcome the limitations of\u00a0ACEIp large\u2010scale production. Latest advances in ACEIp research and current genetic engineering\u2010based strategies for heterologous production of ACEIp (and precursors) are also presented. Cloning approaches include tandem repeats of single ACEIp, ACEIp fusion to proteins\/polypeptides, joining multivariate ACEIp into bioactive polypeptides, and producing ACEIp\u2010containing modified plant storage proteins. Although bacteria have been privileged ACEIp heterologous hosts, particularly when testing for new genetic engineering strategies, plants and microalgae\u2010based platforms are now emerging. Besides being generally safer, cost\u2010effective and scalable, these \u201cpharming\u201d platforms can perform therelevant posttranslational modifications and produce (and eventually deliver) biologically active protein\/peptide\u2010based antihypertensive medicines.<\/jats:p>","DOI":"10.1002\/bit.27373","type":"journal-article","created":{"date-parts":[[2020,5,5]],"date-time":"2020-05-05T08:48:10Z","timestamp":1588668490000},"page":"2610-2628","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Current genetic engineering strategies for the production of antihypertensive ACEI peptides"],"prefix":"10.1002","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1357-353X","authenticated-orcid":false,"given":"Carolina","family":"Gomes","sequence":"first","affiliation":[{"name":"Department of Integrative Plant Biology, Institute of Plant Genetics Polish Academy of Sciences Pozna\u0144 Poland"},{"name":"Plant Cell Biotechnology Laboratory, Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier (ITQB NOVA) Green\u2010it Unit Oeiras Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences (DCM), Institute of Biomedicine (iBiMED) Universidade de Aveiro Aveiro Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3166-450X","authenticated-orcid":false,"given":"Jo\u00e3o P. 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