Abstract
Ganoderma lucidum is widely considered as one of the most valuable Traditional Chinese Medicines, with various bioactive constituents and pharmaceutical effects. Triterpenoids are important effective ingredients of G. lucidum, which are synthesized mainly through the mevalonate pathway. In this study, we aimed to characterize and analyze three committed-step enzymes of the mevalonate pathway, 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase (HMGR), Farnesyl Diphosphate Synthase (FPPS) and Squalene Synthase (SQS), using various bioinformatic tools and servers. As a results, the molecular structures and physicochemical properties of the proteins and their encoding genes (Glhmgr, Glfpps and Glsqs) were studied. The GlHMGR and GlFPPS proteins are localized in the cytosol and lack any transmembrane topological structures. By contrast, GlSQS enters the secretory pathway via its transit peptide and has three transmembrane helices. Phylogenetic analysis suggested that the three proteins could be classified into three large groups according to their significant functional association and genetic conservation. The secondary structures of the GlHMGR, GlFPPS and GlSQS comprise mainly α-helixes and random coils and the three tertiary structures were modeled successfully, including the identification of key motifs. Additionally, the expression levels of the three genes were compared on the basis of dbEST records. In conclusion, the results demonstrated that HMGR, FPPS and SQS from G. Lucidum have typical molecular structures and functions. In addition, we inferred that GlFPPS might be the perfect target for genetic engineering because of its position in a bottleneck step, as revealed by metabolic flux analysis.
Highlights
Isoprenoids are the most abundant natural products, with multiple structures and functions and encompassing more than 30,000 known compounds within the fungus kingdom
Homology-based 3-D modeling of the target proteins was implemented successfully using SWISS-MODEL on the basis of their own corresponding templates: GlHMGR was based on the catalytic portion of human HMG-CoA reductase with HMG, CoA and NADP+; GlFPPS was based on the structure of human farnesyl pyrophosphate synthetase; and GlSQS was based on the crystal structure of human squalene synthase
The subcellular localization and transmembrane helix prediction suggested that GlFPPS and GlSQS were localized in the cytoplasmic matrix and lacked a signal peptide and transmembrane domain
Summary
Isoprenoids are the most abundant natural products, with multiple structures and functions and encompassing more than 30,000 known compounds within the fungus kingdom. As very important metabolites with essential biological functions, isoprenoids are rich in fruit bodies, sporophytes and mycelium to protect these structures from biotic and abiotic stresses, as well as being components of biomembranes and regulators of growth and development (Holstein and Hoh, 2004; Leandro et al., 2012; Liang and Guo, 2013). Research interest in isoprenoids, especially the economically important ones, has increased significantly. Isopreoids are divided into several subgroups, including monoterpenoid C10, sesquiterpenoid C15, diterpenoid C20 and triterpenoid C30, according to the number of C5 units in the skeleton. Triterpenoids comprise six C5 units (Liao et al, 2006a)
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