Effects of lovastin, fosmidomycin and methyl jasmonate on andrographolide biosynthesis in the Andrographis paniculata
- 134 Downloads
Andrographolide is a diterpene secondary metabolite product of Andrographis paniculata. It has been known to be a pharmaceutically important compound synthesized via the cytosolic mevalonate (MVA) and the plastidial 2-C-methyl-d-erythritol-4-phosphate (MEP) pathways. To understand the biosynthetic pathway of andrographolide biosynthesis in Andrographis paniculata, lovastatin, fosmidomycin and methyl jasmonate (MeJA) were used to inhibit the key enzymes 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR), and 1-deoxy-d-xylulose-5-phosphate reducto-isomerase (DXR) involved in the synthesis of andrographolide in the MVA and MEP pathways, respectively. The inhibition of andrographolide accumulation was linked with the expression level of the studied regulatory genes, 3-hydroxy-3-methyl glutaryl coenzyme A synthase (hmgs), 3-hydroxy-3-methyl glutaryl coenzyme A reductase (hmgr), 1-deoxyxylulose-5-phosphate synthase (dxs), 1-deoxyxylulose-5-phosphate reductoisomerase (dxr), 1-hydroxy-2-methyl-2-(E)-butenyl-4-diphosphate synthase (hds),1-hydroxy-2-methyl-2-(E)-butenyl-4-diphosphate reductase (hdr), 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase(isph), isopentenyl diphosphate isomerase (ipp), geranylgeranyl diphosphatesynthase (ggps) of the MVA and MEP pathways. The pathways associated transcript expression level, and andrographolide biosynthesis was significantly modulated by the inhibitors indicating that the andrographolide biosynthesis is strongly responsive at the transcriptional level. The results demonstrated that both pathways can contribute to the biosynthesis of andrographolide in A. paniculata. Both hmgr and dxr played a critical role consistent with some crossover between MVA and MEP pathways in andrographolide biosynthesis.
KeywordsAndrographis paniculata Andrographolide Mevalonate Fosmidomycin Lovastatin Methyl jasmonate
Geranyl geranyl diphosphate
Geranylgeranyl diphosphate synthase
- E HMBPP
3-Hydroxy-3-methyl glutaryl coenzyme A reductase
3-Hydroxy-3-methyl glutaryl coenzyme A synthase
1-Hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase
Financial support from Indira Gandhi Krishi Vishwavidyalaya (IGKV), Raipur is gratefully acknowledged. Thanks to Dr. D.K. Sharma, Former Head, Department of Plant Molecular Biology and Biotechnology for arranging funds and facilities. We thank Jordan Pepper for providing an English proof read.
- Alberts AW, Chen J, Kuron G, Hunt V, Huff J, Hoffman C, Rothrock J, Lopez M, Joshua H, Harris E, Patchett A, Monaghan R, Currie S, Stapley E, Albers-Schonberg G, Hensens O, Hirshfield J, Hoogsteen K, Liesch J, Springer J (1980) Mevinolin: a highly potent competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase and a cholesterol-lowering agent. Proc Natl Acad Sci USA 77:3957–3961CrossRefPubMedGoogle Scholar
- Herz S, Wungsintaweekul J, Schuhr CA, Hecht S, Luttgen H, Sagner S, Fellermeier M, Eisenreich W, Zenk MH, Bacher A, Rohdich F (2000) Biosynthesis of terpenoids: YgbB protein converts 4-diphosphocytidyl-2C-methyl-d-erythritol 2-phosphate to 2C-methyl-d-erythritol 2,4-cyclodiphosphate. Proc Natl Acad Sci USA 97:2486–2490CrossRefPubMedGoogle Scholar
- Hoeffler JF, Hemmerlin A, Grosdemange-Billiard C, Bach TJ, Rohmer M (2002) Isoprenoid biosynthesis in higher plants and in Escherichia coli: on the branching in the methylerythritol phosphate pathway and the independent biosynthesis of isopentenyl diphosphate and dimethylallyl diphosphate. Biochem J 366:573–583CrossRefPubMedPubMedCentralGoogle Scholar
- Sharma SN, Sinha RK, Sharma D, Jha Z (2009) Assessment of intra-specific variability at morphological, molecular and biochemical level of Andrographis paniculata (Kalmegh). Curr Sci 96:402–408Google Scholar
- Singh RS, Gara RK, Bhardwaj PK, Kaachra A, Malik S, Kumar R, Sharma M, Ahuja PS, Kumar S (2010) Expression of 3-hydroxy-3-methylglutaryl-CoA reductase, p-hydroxybenzoate-m-geranyltransferase and genes of phenylpropanoid pathway exhibits positive correlation with shikonins content in arnebia [Arnebia euchroma Royle. Johnston]. BMC Mol Biol 11:88CrossRefPubMedPubMedCentralGoogle Scholar