Isoprenoid biosynthesis: the evolution of two ancient and distinct pathways across genomes

Abstract

Isopentenyl diphosphate (IPP) is the central intermediate in the biosynthesis of isoprenoids, the most ancient and diverse class of natural products. Two distinct routes of IPP biosynthesis occur in nature: the mevalonate pathway and the recently discovered deoxyxylulose 5-phosphate (DXP) pathway. The evolutionary history of the enzymes involved in both routes and the phylogenetic distribution of their genes across genomes suggest that the mevalonate pathway is germane to archaebacteria, that the DXP pathway is germane to eubacteria, and that eukaryotes have inherited their genes for IPP biosynthesis from prokaryotes. The occurrence of genes specific to the DXP pathway is restricted to plastid-bearing eukaryotes, indicating that these genes were acquired from the cyanobacterial ancestor of plastids. However, the individual phylogenies of these genes, with only one exception, do not provide evidence for a specific affinity between the plant genes and their cyanobacterial homologues. The results suggest that lateral gene transfer between eubacteria subsequent to the origin of plastids has played a major role in the evolution of this pathway.

Figure 1

Biosynthesis of IPP via the mevalonate pathway (A) and the DXP pathway (B). The circled P denotes the phosphate moiety. The large open arrow indicates several as yet unidentified steps. Isopentenyl diphosphate isomerase (EC 5.3.3.2) is abbreviated as IPPI.

Figure 2

Phylogenetic relationships of the enzymes of IPP biosynthesis. The trees were constructed by using the protml algorithm (11). The scale bar indicates 100 substitutions for each tree. Dotted ovals indicate that the sequences shown are related to other proteins, but that the positions of the branches by which the families are connected are uncertain. Branches with RELL bootstrap proportions ≥ 0.98 are indicated by a dot. Some of the genes that were detected in supplementary Table 1 are not included in the figure because of discontinuous reading frames.