Jheng-Jhe Lu, Kuan-Chen Cheng, Darin Khumsupan, Chen-Che Hsieh, Chang-Wei Hsieh, Shella Permatasari Santoso, Artik Elisa Angkawijaya, Hsing-Chun Kuo
This study identified angiotensin-converting enzyme (ACE) inhibitory peptides generated during Monascus purpureus fermentation of djulis ( Chenopodium formosanum ). Protein hydrolysates from fermented dehulled djulis showed the highest ACE inhibition, reaching 40.71 ± 2 . 95 % on day 8 (captopril: 43.33 ± 3.53 %). In silico screening (BIOPEP database) and proteomics highlighted DAAGYVADK (DK9) as a potential candidate. Molecular docking indicated a binding affinity of −9.174 kcal/mol (captopril: −5.77). The binding was mainly stabilized by 7 hydrogen bonds with ACE active site residues Glu384, His353, Lys511, Gln281, Asn277, Ala354, and Arg522. Moreover, enzyme-kinetic analysis indicated competitive inhibition by increased K m with unchanged V max. Furthermore, absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions suggested low toxicity and favorable pharmacokinetic properties for DK9. These findings support Monascus -fermented dehulled djulis as a promising substrate to generate natural ACE-inhibitory peptides and identify DK9 as a lead peptide for further development. © 2025 Elsevier Ltd.
Institute of Biotechnology, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd, Taipei, 10617, Taiwan; Department of Optometry, Asia University, No.500, Lioufeng Rd., Wufeng, Taichung, 413305, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University, No. 91, Hsueh-Shih Road, Taichung, 404333, Taiwan; Institute of Food Science and Technology, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd, Taipei, 10617, Taiwan; Department of Food Science, Fu Jen Catholic University, No. 510, Zhongzheng Rd, New Taipei City, 242062, Taiwan; Department of Seafood Science, National Kaohsiung University of Science and Technology, No. 142, Haijhuan Rd., Nanzih District, Kaohsiung, 81157, Taiwan; Department of Food Science and Biotechnology, National Chung Hsing University, 145 Xingda Rd, South Dist, Taichung, 40227, Taiwan; Department of Food Science, National Ilan University, No. 1, Sec. 1, Shennong Rd., Yilan City, 260007, Taiwan; Chemical Engineering Department, Faculty of Engineering, Universitas Katolik Widya Mandala Surabaya, Jl. Kalijudan 37, East Java, Surabaya, 60114, Indonesia; Chemical Engineering Master Program, Universitas Katolik Widya Mandala Surabaya, Jl. Kalijudan 37, East Java, Surabaya, 60114, Indonesia; Collaborative Research Center for Zero Waste and Sustainability, Universitas Katolik Widya Mandala Surabaya, Jl. Kalijudan 37, East Java, Surabaya, 60114, Indonesia; RIKEN Center for Sustainable Resource Science, Yokohama, 230-0045, Japan; Department of Nursing, Division of Basic Medical Sciences, Chang Gung University of Science and Technology, Chiayi, Taiwan; Research Fellow, Chang Gung Memorial Hospital, Chiayi, Taiwan; Center for Drug Research and Development, Chang Gung University of Science and Technology, Taoyuan, Taiwan; Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Chiayi, Taiwan