Recent advances towards development and commercialization of plant cell culture processes for the synthesis of biomolecules.

Recent advances towards development and commercialization of plant cell culture processes for the synthesis of biomolecules.
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DOI:
10.1111/j.1467-7652.2011.00664.x
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发表时间:
2012-04
影响因子:
13.8
通讯作者:
Roberts SC
Roberts SC
中科院分区:
工程技术1区
文献类型:
--
作者:
Wilson SA;Roberts SC

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植物细胞培养系统最初被探索用于商业合成几种高价值的次级代谢产物,允许可持续的生产,而不受与自然收获相关的低产量或与复杂化学合成相关的高成本的限制。虽然已经取得了一些商业上的成功,最显著的是从红豆杉属物种生产紫杉醇,工艺局限性在于低的产品产率和固有的生产可变性。正在开发各种策略来克服这些限制,包括诱导策略,原位产物去除和单基因和转录因子的代谢工程。最近,植物细胞培养生产平台已扩展到具有药物活性的异源蛋白。植物系统是有益的,因为它们能够产生适当糖基化、折叠和组装的复杂蛋白质,而没有被与哺乳动物或微生物生产系统相关的毒素污染的风险。此外,植物细胞培养将转基因材料与环境隔离,允许对田间生长的作物更可控的条件,并促进蛋白质分泌到培养基中,降低下游纯化成本。尽管有这些益处,但与田间生长的作物相比,植物细胞培养物中异源蛋白质合成的成本增加是显著的,因此必须在使分泌最大化和增强细胞培养基中的蛋白质稳定性方面优化工艺。本文综述了植物细胞培养加工技术的最新进展,重点介绍了克服这些生产系统商业化相关问题的进展,并强调了最近的商业成功。
Plant cell culture systems were initially explored for use in commercial synthesis of several high value secondary metabolites, allowing for sustainable production that was not limited by the low yields associated with natural harvest or the high cost associated with complex chemical synthesis. Although there have been some commercial successes, most notably paclitaxel production from Taxus sp., process limitations exist with regards to low product yields and inherent production variability. A variety of strategies are being developed to overcome these limitations including elicitation strategies, in situ product removal and metabolic engineering with single genes and transcription factors. Recently, the plant cell culture production platform has been extended to pharmaceutically active heterologous proteins. Plant systems are beneficial because they are able to produce complex proteins that are properly glycosylated, folded and assembled without the risk of contamination by toxins that are associated with mammalian or microbial production systems. Additionally, plant cell culture isolates transgenic material from the environment, allows for more controllable conditions over field grown crops and promotes secretion of proteins to the medium, reducing downstream purification costs. Despite these benefits, the increase in cost of heterologous protein synthesis in plant cell culture as opposed to field grown crops is significant and therefore processes must be optimized with regards to maximizing secretion and enhancing protein stability in the cell culture media. This review discusses recent advancements in plant cell culture processing technology, focusing on progress towards overcoming the problems associated with commercialization of these production systems and highlighting recent commercial successes.
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