Zhang Kang, Zhao Wenchong, Chen Sheng, Su Lingqia, Wu Jing
State Key Laboratory of Food Science and Resources, Jiangnan University, 1800 Lihu Avenue, Wuxi, 214122, China.
School of Biotechnology and Key Laboratory of Industrial Biotechnology Ministry of Education, Jiangnan University, 1800 Lihu Avenue, Wuxi, 214122, China.
Appl Biochem Biotechnol. 2025 Feb;197(2):926-942. doi: 10.1007/s12010-024-05042-x. Epub 2024 Sep 27.
Sucrose isomerase is an important food enzyme that catalyzes the isomerization of sucrose into isomaltulose, a functional sugar widely used in food industry, while the production level of sucrose isomerase in food safe host strains was much lower than industrial requirement. Bacillus subtilis is an excellent host strain for recombinant protein expression, which owns the characteristics of powerful secretory capability and generally recognized as safe state. In this study, the expression of sucrose isomerase in B. subtilis was improved through expression element optimization and fermentation optimization. Firstly, the extracellular chaperone PrsA was overexpressed to enhance extracellular folding of sucrose isomerase, which improved the recombinant expression level by 80.02%. Then, the protein synthesis level was optimized through promoter screening, improving the recombinant expression level by 60.40%. On the basis of strain modification, the fermentation conditions including nitrogen source, carbon source, metal ion, pH and temperature were optimized successively in shake-flask. Finally, the 3 L bioreactor cultivation condition was optimized and yielding a sucrose isomerase activity of 862.86 U/mL, the highest level among the food safety strains. This study provides an effective strategy to improve the expression level of food enzymes in B. subtilis.
蔗糖异构酶是一种重要的食品酶,可催化蔗糖异构化为异麦芽酮糖醇,异麦芽酮糖醇是一种在食品工业中广泛使用的功能性糖,而在食品安全宿主菌株中蔗糖异构酶的生产水平远低于工业需求。枯草芽孢杆菌是重组蛋白表达的优良宿主菌株,具有强大的分泌能力且通常被认为处于安全状态。在本研究中,通过表达元件优化和发酵优化提高了蔗糖异构酶在枯草芽孢杆菌中的表达。首先,过表达细胞外伴侣蛋白PrsA以增强蔗糖异构酶的细胞外折叠,使重组表达水平提高了80.02%。然后,通过启动子筛选优化蛋白质合成水平,使重组表达水平提高了60.40%。在菌株改造的基础上,在摇瓶中依次优化了包括氮源、碳源、金属离子、pH和温度在内的发酵条件。最后,对3 L生物反应器培养条件进行了优化,获得了862.86 U/mL的蔗糖异构酶活性,这是食品安全菌株中的最高水平。本研究为提高枯草芽孢杆菌中食品酶的表达水平提供了一种有效策略。