Institute of Biology and Soil Science, Far East Branch of Russian Academy of Sciences, Vladivostok, Russia.
Crit Rev Biotechnol. 2012 Sep;32(3):203-17. doi: 10.3109/07388551.2011.596804. Epub 2011 Aug 12.
Rosmarinic acid (RA) is one of the first secondary metabolites produced in plant cell cultures in extremely high yields, up to 19% of the cell dry weight. More complex derivatives of RA, such as rabdosiin and lithospermic acid B, later were also obtained in cell cultures at high yields. RA and its derivatives possess promising biological activities, such as improvement of cognitive performance, prevention of the development of Alzheimer's disease, cardioprotective effects, reduction of the severity of kidney diseases and cancer chemoprevention. The TNF-α-induced NF-κB signaling pathway has emerged as a central target for RA. Despite these impressive activities and high yields, the biotechnological production of these metabolites on an industrial scale has not progressed. We summarized data suggesting that external stimuli, the Ca(2+)-dependent NADPH oxidase pathway and processes of protein phosphorylation/dephosphorylation are involved in the regulation of biosynthesis of these substances in cultured plant cells. In spite of growing information about pathways regulating biosynthesis of RA and its derivatives in cultured plant cells, the exact mechanism of regulation remains unknown. We suggest that further progress in the biotechnology of RA and its derivatives can be achieved by using new high-throughput techniques.
迷迭香酸（RA）是植物细胞培养中最早以极高产量（可达细胞干重的 19%）产生的次级代谢产物之一。后来，在细胞培养中也以高产率获得了 RA 的更复杂衍生物，如瑞诺糖苷和丹参素 B。RA 及其衍生物具有有前途的生物活性，如改善认知表现、预防阿尔茨海默病的发展、心脏保护作用、降低肾脏疾病和癌症化学预防的严重程度。TNF-α 诱导的 NF-κB 信号通路已成为 RA 的一个核心靶点。尽管这些活性很高且产量很高，但这些代谢物的生物技术生产在工业规模上并没有取得进展。我们总结的数据表明，外部刺激、Ca(2+)-依赖性 NADPH 氧化酶途径和蛋白质磷酸化/去磷酸化过程参与了培养植物细胞中这些物质生物合成的调节。尽管关于培养植物细胞中 RA 及其衍生物生物合成的调控途径的信息不断增加，但确切的调控机制仍不清楚。我们建议，通过使用新的高通量技术，可以在 RA 及其衍生物的生物技术方面取得进一步的进展。
