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An improved bioproduction system for proteins and small molecules

改进的蛋白质和小分子生物生产系统

基本信息

批准号：
BB/P010490/1
负责人：
Nicola Joan Patron
金额：
$ 58.54万
依托单位：
Earlham Institute
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2017
资助国家：
英国
起止时间：
2017 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FP010490%2F1
关键词：
improved bioproduction system proteins small

项目摘要

Global demand for quantities of vaccines and therapeutic molecules is growing. Plants, in particular, are the source of a great diversity of biologically active small molecules and a great many natural products found in plants are used as human therapies. However, these chemicals are often found in low abundance or are produced in species that are difficult to mass-cultivate requiring either chemical synthesis or the transfer of the genetic pathway to an alternative biological host in order to produce compounds at sufficient quantities. While microorganisms have proven to be exceptionally powerful for manufacturing therapies, some are not easily produced in high yields. There is particular interest in platforms that are able to respond rapidly to new disease threats, for example, the production of vaccines. Plants have been shown to be capable of efficient expression of therapeutic proteins and secondary metabolites. In a process commonly known as 'molecular pharming' plants have been demonstrated to be capable of producing a very large number of vaccine doses in just a few weeks. Gene expression can be complicated by the endogenous metabolism of the host diverting intermediates or performing unwanted modifications of expressed molecules. Much work has been done to tailor specific strains of bacteria and yeasts to increase production of compounds. However, to date, little effort has been spent on improving the plant production chassis, partly due to a lack of available tools. New technologies now allow us to take targeted approaches to modifying plant genes. We have identified genes expressed by the plant that are likely to be deleterious to heterologous bioproduction of small molecules. We will now make new lines of Nicotiana benthamiana, a relative of tobacco from Northern Australia, that are improved in their ability to produce small molecules of interest. We will then measure the impact of the changes that we have made by assessing the ability of our new lines to produce greater quantities of desirable new proteins and metabolites. This work will add to our knowledge of the metabolism of plants, helping us to understand how it responds to perturbation. It will also lead towards the production of plants that are genetically tailored for the production of different classes of therapeutic molecules

全球对大量疫苗和治疗分子的需求正在增长。尤其是植物，是多种生物活性小分子的来源，植物中的许多天然产物被用作人类的治疗方法。然而，这些化学物质的丰度往往很低，或者是在难以大规模培养的物种中产生的，需要进行化学合成或将遗传途径转移到替代生物宿主，以生产足够数量的化合物。虽然微生物已被证明在制造疗法方面非常强大，但一些微生物不容易高产率地生产。人们对能够对新的疾病威胁做出快速反应的平台特别感兴趣，例如疫苗的生产。植物已被证明能够有效表达治疗性蛋白质和次生代谢物。在通常被称为“分子制药”的过程中，植物已被证明能够在短短几周内生产出非常大量的疫苗剂量。宿主的内源性新陈代谢、转移中间产物或对表达分子进行不必要的修饰可能会使基因表达复杂化。人们已经做了很多工作来定制特定的细菌和酵母菌株，以增加化合物的产量。然而，到目前为止，在改进工厂生产底盘方面投入的努力很少，部分原因是缺乏可用的工具。新技术现在允许我们采取有针对性的方法来修改植物基因。我们已经确定了植物表达的基因，这些基因可能对小分子的异源生物生产有害。我们现在将制造新的烟草品种，一种来自澳大利亚北部的烟草近亲，它们生产感兴趣的小分子的能力得到了改进。然后，我们将通过评估我们的新品系产生更多令人满意的新蛋白质和代谢物的能力来衡量我们所做的变化的影响。这项工作将增加我们对植物新陈代谢的了解，帮助我们了解植物如何对扰动做出反应。它还将导致植物的生产，这些植物是为生产不同类别的治疗分子而定制的基因