Plant polyisoprenoids: Secondary metabolites or physiologically important superlipids?

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，他们最初将其描述为“污染物”。 然而，多年来，这些被称为聚异戊二烯的化合物几乎在所有植物和其他生命王国中都被发现。聚类异戊二烯是五碳（异戊二烯）结构单元的线性聚合物，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，十一萜醇在细菌的细胞壁组装过程中充当脂质载体，而在真核生物中，多萜醇在蛋白质的翻译后修饰中起重要作用。植物除了含有多萜醇外，还含有一组异质的聚异戊二烯，称为聚戊烯醇。 尽管聚戊烯醇在整个植物界中广泛存在，但对其生理作用知之甚少，并且关于参与其形成的酶的问题仍然存在。 同样令人费解的是植物是如何制造多萜醇的，这在动物中也是令人惊讶的不清楚。 因此，该项目的中心重点是更好地了解植物聚异戊二烯生物学。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，分析和生物化学的方法将结合起来，以确定在加拿大农业上重要的作物品种的聚异戊二烯组合物。 第二，比较基因组学将与标准分子技术相结合，以确定和表征合成长萜醇和聚戊烯醇的植物酶。 这些酶被称为顺式异戊二烯基转移酶（CPT）。有趣的是，初步研究表明，多萜醇合成是通过一种机制，这是不同的利用涉及聚戊烯醇生物合成的CPT。我们对长萜醇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类异戊二烯，天然橡胶，新出现的证据表明，天然橡胶与长萜醇的合成具有共同的分子机制。 从本质上讲，这项研究不仅将为研究生提供植物代谢生物化学方面的跨学科培训，而且还将揭示聚异戊二烯生物学这一基本上未被探索的领域。

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.