Ph.D. Program in Microbial Genomics, National Chung Hsing University, 250 Kuo-Kuang Road, Taichung 40227, Taiwan.
Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 11529, Taiwan.
J Agric Food Chem. 2023 Nov 15;71(45):17202-17213. doi: 10.1021/acs.jafc.3c04750. Epub 2023 Oct 31.
An aspartate peptidase with proteolytic activity toward gluten was identified from an isolated red yeast strain. This peptidase consists of 425 amino acids, comprising an N-terminal signal peptide, a propeptide, and a C-terminal catalytic domain. The catalytic domain, termed RmuAP1, could be secreted by the recombinant oleaginous yeast , whose genome contains the expression cassette for RmuAP1. RmuAP1 exhibited optimum activity at pH 2.5 when acting on bovine serum albumin. Moreover, it facilitated the hydrolysis of gluten-derived immunogenic peptides (GIPs), which are responsible for triggering celiac disease symptoms, across a pH range of 3.0-6.0. The preferred cleavage sites are P-Q-Q-↓-P-Q in the 26-mer and P-Q-L-↓-P-Y in the 33-mer GIPs. Conversely, porcine pepsin cannot hydrolyze these two GIPs. The ability of RmuAP1 to degrade GIPs under acidic conditions of the stomach indicates its potential as a viable oral enzyme therapy for celiac disease.
从一株分离的红色酵母菌株中鉴定出一种具有蛋白酶活性的天冬氨酸肽酶。该肽酶由 425 个氨基酸组成，包括 N 端信号肽、前肽和 C 端催化结构域。该催化结构域被称为 RmuAP1，可被重组产油酵母分泌，其基因组包含 RmuAP1 的表达盒。RmuAP1 在作用于牛血清白蛋白时，在 pH2.5 时表现出最佳活性。此外，它能够在 pH3.0-6.0 范围内水解导致乳糜泻症状的谷蛋白衍生免疫原性肽 (GIP)。首选的切割位点是 26 肽中的 P-Q-Q-↓-P-Q 和 33 肽 GIP 中的 P-Q-L-↓-P-Y。相反，猪胃蛋白酶不能水解这两种 GIP。RmuAP1 在胃酸条件下降解 GIP 的能力表明它有作为乳糜泻可行的口服酶治疗的潜力。
