Chemical Phenotypes of the hmg1 and hmg2 Mutants of Arabidopsis Demonstrate the In-planta Role of HMG-CoA Reductase in Triterpene Biosynthesis

Kiyoshi Ohyama, Masashi Suzuki, Kazuo Masuda, Shigeo Yoshida, Toshiya Muranaka
2007 Chemical and pharmaceutical bulletin  
The plant natural products that are derived from squalene can be divided into two groups: steroids derived from cycloartenol (4), such as phytosterols and brassinosteroids, and triterpenoids, such as b-amyrin (1) and lupeol (3) (Fig. 1 ). Phytosterols are highly diverse and are important for plant growth and development as structural components of the plasma membrane and biosynthetic intermediates of brassinosteroids. Recently, lanosterol synthases were identified in several plants. [2] [3] [4]
more » ... Since this new enzyme of sterol backbone synthesis has been identified, the known diversity of phytosterols has increased even more. Triterpenoids are plant-characteristic isoprenoids; they also form a large, structurally diverse group of natural products 5-7) with more than 100 different carbon skeletons. 8) Some have a variety of pharmaco-Plants produce a wide variety of cyclic triterpenes, such as sterols and triterpenoids, which are the major products of the mevalonate (MVA) pathway. It is important to understand the physiological functions of HMG-CoA reductase (HMGR) because HMGR is the rate-limiting enzyme in the MVA pathway. We have previously isolated Arabidopsis mutants in HMG1 and HMG2. Although the biochemical function of HMGR2 has been thought to be almost equal to that of HMGR1, based on similarities in their sequences, the phenotypes of mutants in these genes are quite different. Whereas hmg2 shows no abnormal phenotype under normal growth conditions, hmg1 shows pleiotropic phenotypes, including dwarfing, early senescence, and male sterility. We previously postulated that the 50% decrease in the sterol content of hmg1, as compared to that in the wild type, was a cause of these phenotypes, 1) but comprehensive triterpene profiles of these mutants had not yet been determined. Here, we present the triterpene profiles of hmg1 and hmg2. In contrast to hmg1, hmg2 showed a sterol content 15% lower than that of the wild type. A precise triterpenoid quantification using synthesized deuterated compounds of b b-amyrin (1), a a-amyrin (2), and lupeol (3) showed that the levels of triterpenoids in hmg1 and hmg2 were 65% and 25% lower than in the wild type (WT), respectively. These results demonstrate that HMGR2 as well as HMGR1 is responsible for the biosynthesis of triterpenes in spite of the lack of visible phenotypes in hmg2.
doi:10.1248/cpb.55.1518 pmid:17917299 fatcat:v52i57xxknfudexshc5oc4x22q