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

Haoyue Shu; Qingcui Zhao; Yu Huang; Qiong Shi; Jian Yang

doi:10.1016/j.foodchem.2023.137332

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

Food Chem. 2024 Feb 1:433:137332. doi: 10.1016/j.foodchem.2023.137332. Epub 2023 Sep 3.

Authors

Haoyue Shu¹, Qingcui Zhao², Yu Huang³, Qiong Shi⁴, Jian Yang⁵

Affiliations

¹ School of Food and Drug, Shenzhen Polytechnic University, Shenzhen 518055, China; Postdoctoral Innovation Practice Base, Shenzhen Polytechnic University, Shenzhen 518055, China; State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China. Electronic address: shuhaoyue@szpt.edu.cn.
² School of Food and Drug, Shenzhen Polytechnic University, Shenzhen 518055, China; Postdoctoral Innovation Practice Base, Shenzhen Polytechnic University, Shenzhen 518055, China; State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China. Electronic address: zhaoqingcui@szpt.edu.cn.
³ Shenzhen Key Lab of Marine Genomics, Guangdong Provincial Key Lab of Molecular Breeding in Marine Economic Animals, BGI Academy of Marine Sciences, BGI Marine, Shenzhen 518081, China. Electronic address: huangyu@genomics.cn.
⁴ Shenzhen Key Lab of Marine Genomics, Guangdong Provincial Key Lab of Molecular Breeding in Marine Economic Animals, BGI Academy of Marine Sciences, BGI Marine, Shenzhen 518081, China. Electronic address: shiqiong@genomics.cn.
⁵ School of Food and Drug, Shenzhen Polytechnic University, Shenzhen 518055, China; Postdoctoral Innovation Practice Base, Shenzhen Polytechnic University, Shenzhen 518055, China. Electronic address: jiany@szpt.edu.cn.

PMID: 37683466
DOI: 10.1016/j.foodchem.2023.137332

Abstract

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 μM, 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.

Keywords: Angiotensin-I-converting enzyme; Antihypertensive peptide; Inhibitory mechanism; Molecular docking; RuBisCO.