State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, Guangxi Microorganism and Enzyme Research Center of Engineering Technology, College of Life Science and Technology, Guangxi University, Nanning, China.
State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, Guangxi Microorganism and Enzyme Research Center of Engineering Technology, College of Life Science and Technology, Guangxi University, Nanning, China.
Ultrason Sonochem. 2020 Jun;64:104994. doi: 10.1016/j.ultsonch.2020.104994. Epub 2020 Jan 30.
Anticoagulants are the main drugs for the prevention and treatment of thromboembolism. However, most of the present anticoagulants have shortcomings and novel anticoagulants are in great demand. Marine microorganisms are an important source of new drugs. Therefore, in this study, ultrasound was applied to enhance anticoagulant accumulation by marine Bacillus subtilis ZHX. Ultrasound parameters were optimized by single-factor experiments exploring the effects of ultrasound power, duration, duty cycle and the cell growth phases. The optimum conditions were exponential prophase (5 h) with 25 kHz frequency, 140 W power, and a 40% duty cycle for 5 min. The maximum anticoagulant activity (55.36 U/mL) was 1.73 times that of the control group, and the fermentation time was shortened by 3 h. Under optimal conditions, ultrasound increased the carbon utilization by Bacillus subtilis ZHX without significant changes in morphology, favoring cell growth and anticoagulant production. However, excessive ultrasound caused intracellular damage, which inhibited biomass accumulation, decreasing anticoagulant activity and even leading to cell rupture. This is the first report on the use of ultrasound to enhance anticoagulant production by Bacillus, and it provides useful information for scaling-up the process.
抗凝血剂是预防和治疗血栓栓塞的主要药物。然而，大多数现有的抗凝血剂都有缺点，因此急需新型抗凝血剂。海洋微生物是新药的重要来源。因此，在这项研究中，应用超声波增强海洋枯草芽孢杆菌 ZHX 的抗凝血剂积累。通过单因素实验探索超声功率、作用时间、占空比和细胞生长阶段对抗凝血剂活性的影响，优化了超声参数。最佳条件为 25 kHz 频率、140 W 功率和 40%占空比的指数前期（5 h）作用 5 min。最大抗凝血活性（55.36 U/mL）是对照组的 1.73 倍，发酵时间缩短了 3 h。在最佳条件下，超声波增加了枯草芽孢杆菌 ZHX 的碳利用率，而形态没有明显变化，有利于细胞生长和抗凝血剂的产生。然而，过度的超声会导致细胞内损伤，抑制生物量的积累，降低抗凝血活性，甚至导致细胞破裂。这是首次报道利用超声波增强枯草芽孢杆菌的抗凝血剂生产，为该过程的放大提供了有用的信息。
