Current Genetic Engineering Strategies for the Production of Anti‐Hypertensive Acei Peptides

: Hypertension is a major and highly prevalent risk factor for various diseases. Among most frequently prescribed antihypertensive first-line drugs are synthetic angiotensin I-converting enzyme inhibitors (ACEI). However, since their use in hypertension therapy has been linked to various side effects, the interest on the potential of food-derived ACEI peptides (ACEIp) as antihypertensive agents is rapidly growing. Although promising, the industrial production of ACEIp through conventional methods as chemical synthesis or enzymatic hydrolysis of food proteins has been proven troublesome. We here provide an overview on current antihypertensive therapeutics, focusing on ACEI, and illustrate how biotechnology and bioengineering can overcome limitations to the large-scale production of ACEIp. Latest advances on ACEIp research and current engineer-based strategies for heterologous production of ACEIp (and precursors) are also presented and discussed. Approaches include tandem repeats of one type of ACEIp, ACEIp fusion to proteins/polypeptides, joining multivariate ACEIp into bioactive polypeptides, and producing ACEIp-containing modified plant storage proteins. Indeed, although bacteria have been privileged heterologous hosts, particularly when testing for new genetic engineering strategies, plants and microalgae-based platforms are now emerging. Besides generally safer, cost-effective and scalable, these 'pharming' platforms can perform relevant post-translational modifications and to produce (and eventually deliver) biologically active protein/peptide-based medicines. This article is protected by copyright. All rights reserved.