Gaid Mariam, Grosch Jan-Hendrik, Möller Steve, Beerhues Ludger, Krull Rainer
Institute of Pharmaceutical Biology Technische Universität Braunschweig Braunschweig Germany.
Center of Pharmaceutical Engineering (PVZ) Technische Universität Braunschweig Braunschweig Germany.
Eng Life Sci. 2019 Jun 4;19(12):916-930. doi: 10.1002/elsc.201900043. eCollection 2019 Dec.
During the past decades, several trials targeted a stable, sustainable and economic production of St. John's wort () extract. The value of this extract stems from its use to treat depression and skin irritation due to its hyperforin content. Previously, hyperforin-forming root cultures were established. Here, detailed growth and production kinetics have been analyzed over 40 days of cultivation. In the first 10 days, sucrose was completely hydrolyzed to glucose and fructose. The ammonium consumption supported the increase in the biomass and hyperforin production. When sucrose was replaced with glucose/fructose, the linear growth phase started 6 days earlier and resulted in a higher space-time-yield. The maximum hyperforin production was 0.82 mg L day, which was 67 % higher than in the sucrose-supplemented standard cultivation. Buffering the sucrose-supplemented medium with phosphate caused a 2.7-fold increase in the product to biomass yield coefficient. However, the combination of monosaccharides and buffering conditions did not cause an appreciable improvements in the production performance of the shake flask approaches. A potential scalability from flask to lab-scale stirred bioreactors has been demonstrated. The results obtained offer a basis for a scalable production of hyperforin and a sustainable source for a tissue culture-based phytomedicine.
在过去几十年里,有多项试验旨在稳定、可持续且经济地生产圣约翰草提取物。这种提取物的价值源于其可用于治疗抑郁症和皮肤刺激,因为它含有金丝桃素。此前,已建立了能形成金丝桃素的根培养物。在此,对40天培养期内的详细生长和生产动力学进行了分析。在最初的10天里,蔗糖完全水解为葡萄糖和果糖。铵的消耗促进了生物量和金丝桃素产量的增加。当用葡萄糖/果糖替代蔗糖时,线性生长阶段提前6天开始,且时空产率更高。金丝桃素的最大产量为0.82毫克/升·天,比补充蔗糖的标准培养高出67%。用磷酸盐缓冲补充蔗糖的培养基可使产物与生物量的产率系数提高2.7倍。然而,单糖与缓冲条件的组合并未使摇瓶培养法的生产性能有明显改善。已证明了从摇瓶到实验室规模搅拌式生物反应器的潜在可扩展性。所获得的结果为金丝桃素的可扩展生产以及基于组织培养的植物药的可持续来源提供了基础。