Ade Carina, Marcelino Thaís F, Dulchavsky Mark, Wu Kevin, Bardwell James C A, Städler Brigitte
Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, Aarhus, 8000, Denmark.
Sino-Danish Center for Education and Research, University of Chinese Academy of Sciences, China.
Mater Adv. 2022 Apr 21;3(8):3649-3662. doi: 10.1039/d2ma00051b. Epub 2022 Mar 29.
Extremophile enzymes are useful in biotechnology and biomedicine due to their abilities to withstand harsh environments. The abilities of histidine ammonia lyases from different extremophiles to preserve their catalytic activities after exposure to acid were assessed. histidine ammonia lyase was identified as an enzyme with a promising catalytic profile following acid treatment. The fusion of this enzyme with the maltose-binding protein or co-incubation with the chaperone HdeA further helped histidine ammonia lyase to withstand acid treatments down to pH 2.8. The assembly of a microreactor by encapsulation of MBP- histidine ammonia lyase into a photocrosslinked poly(vinyl alcohol) hydrogel allowed the enzyme to recover over 50% of its enzymatic activity following exposure to simulated gastric and intestinal fluids. Our results show that using engineered proteins obtained from extremophiles in combination with polymer-based encapsulation can advance the oral formulations of biologicals.
嗜极端微生物酶因其能够耐受恶劣环境而在生物技术和生物医学中具有重要用途。我们评估了来自不同嗜极端微生物的组氨酸氨裂解酶在暴露于酸性环境后保持其催化活性的能力。经酸处理后,组氨酸氨裂解酶被鉴定为具有良好催化特性的一种酶。该酶与麦芽糖结合蛋白融合或与伴侣蛋白HdeA共孵育,进一步帮助组氨酸氨裂解酶耐受低至pH 2.8的酸处理。通过将麦芽糖结合蛋白-组氨酸氨裂解酶封装到光交联聚乙烯醇水凝胶中来组装微反应器,使得该酶在暴露于模拟胃液和肠液后能够恢复超过50%的酶活性。我们的结果表明,将来自嗜极端微生物的工程蛋白与基于聚合物的封装相结合,可以推动生物制剂的口服制剂发展。