Plant polyisoprenoids: Secondary metabolites or physiologically important superlipids?

植物聚异戊二烯：次生代谢物还是生理上重要的超脂？

• 批准号: RGPIN-2014-05628
• 负责人: Akhtar, Tariq
• 金额: $ 2.11万
• 依托单位: University of Guelph
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=567287
• 关键词: Plant; polyisoprenoids; Secondary; metabolites; physiologically

Just over 50 years ago, scientists discovered a group of compounds in the extracts of birch wood which they originally described as ‘contaminants’. Yet over the years these same compounds, known as polyisoprenoids, have been found in virtually all plants and in other kingdoms of life. Polyisoprenoids are linear polymers of five-carbon (isoprene) building blocks that we now know serve indispensable roles in both prokaryotes and eukaryotes. For example, undecaprenol acts as a lipid carrier during cell wall assembly in bacteria, while in eukaryotes, dolichol plays an essential role in the post-translational modification of proteins. Plants contain, in addition to dolichol, a heterogeneous group of polyisoprenoids known as polyprenols. In spite of the widespread occurrence of polyprenols throughout the plant kingdom, little is known about their physiological role, and questions still remain about the enzymes that are involved in their formation. Equally enigmatic is how plants make dolichol, which is surprisingly unclear in animals as well. Accordingly, the central focus of this project is to gain a better understanding of plant polyisoprenoid biology. Building on our recent work, the research outlined in this proposal has three specific aims. First, analytical and biochemical approaches will be combined to define the polyisoprenoid composition in Canadian agriculturally important crop species. Second, comparative genomics will be coupled with standard molecular techniques in order to identify and characterize the plant enzymes that synthesize dolichol and polyprenols. These enzymes are known as cis-prenyltransferases (CPTs). Intriguingly, pilot studies indicate that dolichol synthesis proceeds via a mechanism which is distinct from that utilized by the CPTs implicated in polyprenol biosynthesis. Our understanding of dolichol biosynthesis will then be applied towards our third and final aim which will be to synthesize the world’s most significant polyisoprenoid, natural rubber, which newly emerging evidence suggests shares a common molecular mechanism of synthesis with that of dolichol. Essentially, the proposed research will not only provide cross-disciplinary training in plant metabolic biochemistry to graduate students, but will also shed light onto the largely unexplored area of polyisoprenoid biology.

就在50多年前，科学家们在桦木提取物中发现了一组化合物，他们最初将其称为“污染物”。然而，多年来，在几乎所有的植物和其他生命领域中都发现了这些被称为类多异戊二烯的化合物。聚异戊二烯类是五碳（异戊二烯）的线性聚合物，我们现在知道它在原核生物和真核生物中都起着不可或缺的作用。例如，在细菌的细胞壁组装过程中，去戊烯醇作为脂质载体，而在真核生物中，醇在蛋白质的翻译后修饰中起着至关重要的作用。植物除了含有醇外，还含有异质的类聚异戊二烯，称为聚戊烯醇。尽管聚戊烯醇在植物界广泛存在，但对其生理作用知之甚少，对其形成所涉及的酶仍然存在疑问。同样令人费解的是，植物是如何制造乙醇的，这在动物身上也令人惊讶地不清楚。因此，本项目的中心重点是更好地了解植物类聚异戊二烯生物学。在我们最近工作的基础上，本提案中概述的研究有三个具体目标。首先，将结合分析和生化方法来确定加拿大农业上重要作物物种的聚异戊二烯组成。其次，比较基因组学将与标准分子技术相结合，以鉴定和表征合成乙醇和聚戊烯醇的植物酶。这些酶被称为顺-戊烯基转移酶（cpt）。有趣的是，初步研究表明，聚戊二醇合成的机制与聚戊二醇生物合成中涉及的cpt所利用的机制不同。我们对醇类生物合成的理解将应用于我们的第三个也是最后一个目标，即合成世界上最重要的聚异戊二烯类天然橡胶，新出现的证据表明，它与醇类具有共同的分子合成机制。从本质上讲，拟议的研究不仅将为研究生提供植物代谢生物化学的跨学科培训，而且还将为尚未开发的聚异戊二烯生物学领域提供启发。