植物系统中生物碱代谢工程的最新进展。
Recent progress in the metabolic engineering of alkaloids in plant systems.
机构信息
John Innes Centre, Department of Biological Chemistry, Norwich Research Park, Norwich NR4 7UH, UK.
出版信息
Curr Opin Biotechnol. 2013 Apr;24(2):354-65. doi: 10.1016/j.copbio.2012.08.003. Epub 2012 Sep 3.
Abstract
Plant alkaloids have a rich chemical ecology that has been exploited for medicinal purposes for thousands of years. Despite being highly represented within today's pharmacopoeia, relatively little is known about the biosynthesis, regulation and transport of these molecules. Understanding how nature synthesizes plant alkaloids will enhance our ability to overproduce--that is, to metabolically engineer--these medicinally useful compounds as well as new-to-nature compounds (with potentially improved bioactivity) derived from these natural scaffolds. Recent progress in the metabolic engineering of nitrogen-containing plant natural products--specifically the monoterpene indole alkaloids, the benzylisoquinoline alkaloids and the glucosinolates--was made possible through the characterization of various components in both native and engineered enzymatic pathways. The subsequent reconfiguration and tuning of these biological 'parts' has enabled the production of selected products at increasingly higher titers.
摘要
植物生物碱具有丰富的化学生态，几千年来一直被用于医学用途。尽管它们在当今的药典中得到了广泛的应用，但对于这些分子的生物合成、调控和运输却知之甚少。了解大自然如何合成植物生物碱，将提高我们大量生产——即代谢工程——这些药用化合物以及从这些天然支架衍生而来的新型天然化合物（具有潜在改善的生物活性）的能力。通过对天然和工程化酶途径中的各种成分进行表征，使得含氮植物天然产物（特别是单萜吲哚生物碱、苯并异喹啉生物碱和硫代葡萄糖苷）的代谢工程取得了最近的进展。随后对这些生物“部件”进行重新配置和调整，使得选定产物的产量不断提高。
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