Antihypertensive peptide resources map of ribulose-1,5-bisphosphate carboxylase/oxygenases (RuBisCO) in angiosperms: Revealed by an integrated in silico and in vitro approach

As the most abundant protein on earth, ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) has been considered a promising resource of functional foods. This study aimed to explore the full potential of plant RuBisCO proteins as precursors of antihypertensive peptides on a large scale. In total, 12,766 RuBisCO large subunit and 1,020 RuBisCO small subunit sequences of angiosperms were collected for simulated proteolysis and evaluation of antihypertensive potential, revealing a vast reservoir of antihypertensive peptides. Moreover, RuBisCO-derived novel antihypertensive peptides TTVW, TMW, and VPCL were identified with in vitro IC50 of 12.89 +/- 0.82, 23.97 +/- 1.02, and 339.12 +/- 21.64 mu M, respectively. Notably, TTVW and TMW are noncompetitive inhibitors predicted to bound adjacent to the catalytic region of ACE, while VPCL is a competitive inhibitor predicted to bound to the central active site inside ACE. Overall, this work provides a powerful theoretical guidance in developing antihypertensive functional foods utilizing plant RuBisCO.