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重组微生物中经济相关植物次生代谢产物的途径重建与生产工具。

Tools of pathway reconstruction and production of economically relevant plant secondary metabolites in recombinant microorganisms.

作者信息

Dziggel Clarissa, Schäfer Holger, Wink Michael

机构信息

Heidelberg University, Institute of Pharmacy and Molecular Biotechnology, Heidelberg, Germany.

出版信息

Biotechnol J. 2017 Jan;12(1). doi: 10.1002/biot.201600145. Epub 2016 Dec 23.

Abstract

Plant secondary metabolites exhibit a variety of biological activities and therefore serve as valuable therapeutics or flavoring compounds. However, the small amounts isolated from plants often cannot meet market demands. This led to the exploration of other, more profitable methods for their production, including plant cell culture systems, chemical synthesis and biotechnological production in microbial hosts. The biotechnological production can be pursued by reconstructing metabolic pathways in selected microbial systems. But due to their complexity, most of these pathways are not completely understood and require the expression of a multitude of genes in a foreign organism. Recently, next generation sequencing data and advances in gene silencing in plants allowed the elucidation of some biosynthetic pathways in more detail. Thus, the de novo production of some natural products, including morphine, strictosidine, artemisinin, taxol and resveratrol, in extensively engineered microbial hosts has become feasible. This review highlights the reconstruction of these pathways, missing pieces and novel techniques employed.

摘要

植物次生代谢产物具有多种生物活性,因此可作为有价值的治疗药物或调味化合物。然而,从植物中分离出的少量产物往往无法满足市场需求。这促使人们探索其他更具盈利性的生产方法,包括植物细胞培养系统、化学合成以及在微生物宿主中的生物技术生产。生物技术生产可以通过在选定的微生物系统中重建代谢途径来实现。但由于这些途径的复杂性,其中大多数尚未被完全理解,并且需要在异源生物体中表达多个基因。最近,下一代测序数据以及植物基因沉默技术的进展使得一些生物合成途径能够得到更详细的阐明。因此,在经过广泛工程改造的微生物宿主中从头生产某些天然产物,包括吗啡、长春花苷内酰胺、青蒿素、紫杉醇和白藜芦醇,已变得可行。本综述重点介绍了这些途径的重建、缺失环节以及所采用的新技术。

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