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同源和异源体系中天南星单萜吲哚生物碱工程的现状。

Present status of Catharanthus roseus monoterpenoid indole alkaloids engineering in homo- and hetero-logous systems.

机构信息

C. G. Bhakta Institute of Biotechnology, Uka Tarsadia University, Gopal-Vidyanagar, Maliba Campus, Surat, 394350, India.

Department of Plant Biotechnology, Central Institute of Medicinal and Aromatic Plants (CIMAP), Council of Scientific and Industrial Research, PO CIMAP, Lucknow, 226015, India.

出版信息

Biotechnol Lett. 2020 Jan;42(1):11-23. doi: 10.1007/s10529-019-02757-4. Epub 2019 Nov 15.

Abstract

Catharanthus roseus synthesizes one of the most structurally, chemically and biologically active phytomolecules monoterpenoids indole alkaloids (MIAs) with having a wide range of pharmaceutical activities. Being the sole source of antineoplastic MIAs vinblastine and vincristine C. roseus has become one of the most valued plant. The low in planta availability of these MIAs and unavailability of alternative chemical synthesis system has enhanced their demand and equally let to the exorbitant market cost. To bridge this gap alternative production systems have been investigated using MIAs metabolic engineering (ME) in the homologous and heterologous systems. The availability of improved recombinant technologies along with genomics and metabolomics tools has opened the door of tremendous new potentials of ME. To encash these potentials of ME for MIAs pathway, efforts were made by expressing constitutive structure biosynthesis enzymes, transporters, and transcription factors of C. roseus MIAs biosynthesis in both homologous and heterologous systems. Here we review the knowledge of C. roseus MIAs pathway metabolic engineering in homologous and heterologous systems, gained in the past 35 years of C. roseus research.

摘要

长春花合成了具有广泛药用活性的结构、化学和生物活性均为单萜吲哚生物碱(MIAs)的植物分子之一。长春花是抗肿瘤 MIA 长春碱和长春新碱的唯一来源,已成为最有价值的植物之一。这些 MIA 在植物体内的含量低,且没有替代的化学合成系统,这增加了它们的需求,也导致了过高的市场成本。为了弥补这一差距,人们已经在同源和异源系统中使用 MIA 的代谢工程(ME)来研究替代的生产系统。随着重组技术的改进,以及基因组学和代谢组学工具的出现,为 ME 带来了巨大的新潜力。为了利用 ME 在 MIA 途径中的这些潜力,人们通过在同源和异源系统中表达长春花 MIA 生物合成的组成型结构生物合成酶、转运蛋白和转录因子,来推动 MIA 途径的 ME。在这里,我们回顾了过去 35 年来长春花研究中在同源和异源系统中对长春花 MIA 途径代谢工程的认识。

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