Kuang Xue-Jun, Wang Cai-Xia, Zou Li-Qiu, Zhu Xiao-Xuan, Sun Chao
Institute of Medicinal Plant Development, China Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Zhongguo Zhong Yao Za Zhi. 2016 Nov;41(22):4129-4137. doi: 10.4268/cjcmm20162208.
Catharanthus roseus can produce a variety of terpenoid indole alkaloids (TIA), most of which exhibit strong pharmacological activities. Hence, biosynthesis and regulation of TIA have received recent attention. 3α (S)-strictosidine is an important node in TIA biosynthesis, which is a condensation product of secologanin and tryptamine. The former is produced in iridoid pathway, and the latter is produced in indole pathway. Vindoline and catharanthine, which are produced respectively by 3α (S)-strictosidine via multi-step enzymatic reaction, can form α-3, 4-anhydrovinblastine by the condensation reaction. Then, vinblastine and vincristine are generated from α-3, 4-anhydrovinblastine. Many transcription factors are involved in the regulation of TIA synthesis, such as AP2/ERF and WRKY. Illumination of biosynthetic pathway has laid a foundation for the study of synthetic biology. Today, 3α (S)-strictosidine and vindoline have been synthesized in heterologous hosts Saccharomyces cerevisiae.Research about synthetic biology and the regulation mechanisms will provide a guidance for the production and development of TIA drugs in C. roseus.
长春花能够产生多种萜类吲哚生物碱(TIA),其中大多数具有很强的药理活性。因此,TIA的生物合成和调控受到了近期的关注。3α(S)-异胡豆苷是TIA生物合成中的一个重要节点,它是裂环马钱子苷和色胺的缩合产物。前者在环烯醚萜途径中产生,后者在吲哚途径中产生。3α(S)-异胡豆苷通过多步酶促反应分别产生的文多灵和长春质碱,可通过缩合反应形成α-3,4-脱水长春碱。然后,从α-3,4-脱水长春碱生成长春碱和长春新碱。许多转录因子参与TIA合成的调控,如AP2/ERF和WRKY。生物合成途径的阐明为合成生物学的研究奠定了基础。如今,3α(S)-异胡豆苷和文多灵已在异源宿主酿酒酵母中合成。关于合成生物学及其调控机制的研究将为长春花中TIA药物的生产和开发提供指导。