In silico Analysis of three Committed-Steps Involved in Triterpenoid Biosynthesis from Ganoderma lucidum
Xiaorong Shui, Xiaozhong Lan and Wei Lei
DOI : 10.3844/ajbbsp.2016.171.178
American Journal of Biochemistry and Biotechnology
Volume 12, Issue 3
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.
© 2016 Xiaorong Shui, Xiaozhong Lan and Wei Lei. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.