• Title/Summary/Keyword: MVA pathway

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Triterpenoid Ginsenoside Biosynthesis in Panax ginseng C. A. Meyer (인삼에서의 트리터페노이드 진세노사이드의 생합성)

  • Kim, Yu-Jin;Lee, Ok-Ran;Yang, Deok-Chun
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2012.05a
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    • pp.20-20
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    • 2012
  • Isoprenoids represent the most diverse group of metabolites, which are functionally and structurally identified in plant organism to date. Ginsenosides, glycosylated triterpenes, are considered to be the major pharmaceutically active ingredient of ginseng. Its backbones, categorized as protopanaxadiol (PPD), protopanaxatriol (PPT), and oleanane saponin, are synthesized via the isoprenoid pathway by cyclization of 2,3-oxidosqualene mediated with dammarenediol synthase or beta-amyrin synthase. The rate-limiting 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), which is the first committed step enzyme catalyzes the cytoplasmic mevalonate (MVA) pathway for isoprenoid biosynthesis. DXP reductoisomerese (DXR), yields 2-C-methyl-D-erythritol 4-phosphate (MEP), is partly involved in isoprenoid biosynthesis via plastid. Squalene synthase and squalene epoxidase are involved right before the cyclization step. The triterpene backbone then undergoes various modifications, such as oxidation, substitution, and glycosylation. Here we will discuss general biosynthesis pathway for the production of ginsenoside and its modification based on their subcellular biological functions.

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Apo-1/Fas (CD95) Gene Polymorphism in Korean Knee Osteoarthritis Patients (한국인 무릎 골 관절염 환자들의 임상 양상과 Apo-1/Fas (CD95) 유전자 다형성과의 상관관계에 관한 연구)

  • Hong, Seung-Jae;Yang, Hyung-In;Yim, Sung-Vin;Chung, Joo-Ho;Jung, Young-Ok;Kim, Ho-Youn
    • IMMUNE NETWORK
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    • v.3 no.2
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    • pp.145-149
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    • 2003
  • Background: Apoptosis has been implicated in pathogenesis of various disease. Apo-1/Fas (CD95) is one of the main pathway of apoptosis. To examine the possible relationship between Apo-1/Fas (CD95) and primary knee osteoarthritis, MvaI restriction length polymorphism (RFLP) in human Apo-1/Fas (CD95) gene was assessed. Methods: Genotype and allele frequencies in promoter region in the Apo-1/Fas (CD95) gene were studied by PCR-RFLP in 226 Korean controls and 148 Korean patients with primary knee osteoarthritis. Results: No statistically significant difference in the genotypic distribution and allelic frequencies was found between the control and the knee oateoarthritis patients. But in the severe grade (grade 3, 4) Kellgren-Lawrence score patients, the frequency of $MvaI^*1$ (G) allele was significantly decreased (P=0.0392) and the of $MvaI^*2$ (A) allele frequency was significantly increased (P=0.0473) compared to the normal controls. Conclusion: Apo-1/Fas (CD95) gene polymorphism is a part a determinant factor of severity in knee osteoarthritis, the patients with $MvaI^*2$ (A) allele is more severe radiologic progression. Further substantiation studies are needed in larger patient samples and various other apoptosis related genes to elucidate the mechanism of osteoarthritis, including the Fas ligand gene analysis.

Production of Bio-Based Isoprene by the Mevalonate Pathway Cassette in Ralstonia eutropha

  • Lee, Hyeok-Won;Park, Jung-Ho;Lee, Hee-Seok;Choi, Wonho;Seo, Sung-Hwa;Anggraini, Irika Devi;Choi, Eui-Sung;Lee, Hong-Weon
    • Journal of Microbiology and Biotechnology
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    • v.29 no.10
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    • pp.1656-1664
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    • 2019
  • Isoprene has the potential to replace some petroleum-based chemicals and can be produced through biological systems using renewable carbon sources. Ralstonia eutropha can produce value-added compounds, including intracellular polyhydroxyalkanoate (PHA) through fatty acid and lipid metabolism. In the present study, we engineered strains of R. eutropha H16 and examined the strains for isoprene production. We optimized codons of all the genes involved in isoprene synthesis by the mevalonate pathway and manipulated the promoter regions using pLac and pJ5 elements. Our results showed that isoprene productivity was higher using the J5 promoter ($1.9{\pm}0.24{\mu}g/l$) than when using the lac promoter ($1.5{\pm}0.2{\mu}g/l$). Additionally, the use of three J5 promoters was more efficient ($3.8{\pm}0.18{\mu}g/l$) for isoprene production than a one-promoter system, and could be scaled up to a 5-L batch-cultivation from a T-flask culture. Although the isoprene yield obtained in our study was insufficient to meet industrial demands, our study, for the first time, shows that R. eutropha can be modified for efficient isoprene production and lays the foundation for further optimization of the fermentation process.

Advances in Biochemistry and Microbial Production of Squalene and Its Derivatives

  • Ghimire, Gopal Prasad;Nguyen, Huy Thuan;Koirala, Niranjan;Sohng, Jae Kyung
    • Journal of Microbiology and Biotechnology
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    • v.26 no.3
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    • pp.441-451
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    • 2016
  • Squalene is a linear triterpene formed via the MVA or MEP biosynthetic pathway and is widely distributed in bacteria, fungi, algae, plants, and animals. Metabolically, squalene is used not only as a precursor in the synthesis of complex secondary metabolites such as sterols, hormones, and vitamins, but also as a carbon source in aerobic and anaerobic fermentation in microorganisms. Owing to the increasing roles of squalene as an antioxidant, anticancer, and anti-inflammatory agent, the demand for this chemical is highly urgent. As a result, with the exception of traditional methods of the isolation of squalene from animals (shark liver oil) and plants, biotechnological methods using microorganisms as producers have afforded increased yield and productivity, but a reduction in progress. In this paper, we first review the biosynthetic routes of squalene and its typical derivatives, particularly the squalene synthase route. Second, typical biotechnological methods for the enhanced production of squalene using microbial cell factories are summarized and classified. Finally, the outline and discussion of the novel trend in the production of squalene with several updated events to 2015 are presented.

Molecular Cloning and Functional Analysis of the Gene Encoding 3-hydroxy-3-methylglutaryl Coenzyme A Reductase from Hazel (Corylus avellana L. Gasaway)

  • Wang, Yechun;Guo, Binhui;Zhang, Fei;Yao, Hongyan;Miao, Zhiqi;Tang, Kexuan
    • BMB Reports
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    • v.40 no.6
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    • pp.861-869
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    • 2007
  • The enzyme 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR; EC1.1.1.34) catalyzes the first committed step of isoprenoids biosynthesis in MVA pathway. Here we report for the first time the cloning and characterization of a full-length cDNA encoding HMGR (designated as CgHMGR, GenBank accession number EF206343) from hazel (Corylus avellana L. Gasaway), a taxol-producing plant species. The full-length cDNA of CgHMGR was 2064 bp containing a 1704-bp ORF encoding 567 amino acids. Bioinformatic analyses revealed that the deduced CgHMGR had extensive homology with other plant HMGRs and contained two transmembrane domains and a catalytic domain. The predicted 3-D model of CgHMGR had a typical spatial structure of HMGRs. Southern blot analysis indicated that CgHMGR belonged to a small gene family. Expression analysis revealed that CgHMGR expressed high in roots, and low in leaves and stems, and the expression of CgHMGR could be up-regulated by methyl jasmonate (MeJA). The functional color assay in Escherichia coli showed that CgHMGR could accelerate the biosynthesis of $\beta$-carotene, indicating that CgHMGR encoded a functional protein. The cloning, characterization and functional analysis of CgHMGR gene will enable us to further understand the role of CgHMGR involved in taxol biosynthetic pathway in C. avellana at molecular level.