Plant polyisoprenoids: Secondary metabolites or physiologically important superlipids?

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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.