Metal-chelating peptides, which form metal-peptide coordination complexes with various metal ions, can be used as biofunctional ingredients notably to enhance human health and prevent diseases. This review aims to discuss recent insights into food-derived metal-chelating peptides, the strategies set up for their discovery, their study, and identification. After understanding the overall properties of metal-chelating peptides, their production from food-derived protein sources and their potential applications will be discussed, particularly in nutrition, cosmetic and pharmaceutical fields. In addition, the review provides an overview of the last decades progress in discovering food-derived metal-chelating peptides, addressing several screening, separation and identification methodologies. Furthermore, it emphasizes on the methods used to assess the peptide-metal interaction, allowing for better understanding of chemical and thermodynamic parameters associated to the formation of peptide-metal coordination complexes, as well as the specific amino acid residues that play important roles in the metal ion coordination.

MCPs are biofunctional peptides that interact with metal ions and forming peptide-metal complexes. Considering such ability of peptides and the numerous roles of metals in biological processes, many studies in the literature have demonstrated that these MCPs provide positive health outcomes. For instance, due to the complexation with various metals (such as divalent ions Ca 2+ , Zn 2+ , Fe 2+ and Cu 2+ ) endowed with important biological functions, MCPs promote better stability, absorption, and bioavailability of these minerals 3,4 ; thus, they can eventually be used as nutraceutical compounds for mitigating mineral deficiency and related health problems and overcome the drawbacks of mineral supplement salts in the market. Besides, angiotensin-converting enzyme (ACE) is a Zn 2+dependent enzyme involved in hypertension, with zinc ion playing an important role in the active site. It has been reported that the binding of peptides to Zn 2+ might move the zinc ion away from the active site, resulting in a change in the conformation of the active site and eventually ACE inhibition. 5 Thus, MCPs capable of binding the zinc cofactor could potentially possess ACE inhibitory activity and be used as antihypertensive compounds. 6 MCPs can also act as indirect antioxidants while complexing transition metal ions (i.e., Fe 2+ and Cu 2+ ) 7 , preventing oxidative damage and related chronic disease conditions. 8 Indeed, free Fe 2+ and Cu 2+ can generate reactive oxygen species (ROS) via the Fenton and Haber-Weiss reactions. These ROS are responsible for radical chain reaction, inducing biomolecules damages and, thus, degenerative, neurological, cardiovascular, and cancer diseases. 9

In the global context of food protein-derived hydrolysates, MCPs are produced either from matrices of animal origin (e.g., milk, eggs, meat and fish), or from vegetable sources, such as soybeans, wheat, and many other legumes and cereals. 10 However, in recent years, several studies on the production of MCPs have emphasized on the use of agro-industrial byproducts as protein sources of BAPs due to low environmental impacts of their production, high protein content, and potentially high-added value after by-products valorisation. 11 Once the protein source is selected, MCPs can be released from their protein precursors by in vitro hydrolysis (enzymatic, fermentative) or by gastrointestinal digestion. 12,13 Then, following the classic empirical approach, hydrolysates are processed based on their structural and physicochemical properties. 14 Separation and purification techniques generally