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Effects of lovastin, fosmidomycin and methyl jasmonate on andrographolide biosynthesis in the Andrographis paniculata

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Abstract

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.

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Abbreviations

DMAPP:

Dimethylallyl diphosphate

DXP:

1-Deoxy-d-xylulose-5-phosphate

dxr:

1-Deoxyxylulose-5-phosphate reductoisomerase

dxs:

1-Deoxyxylulose-5-phosphate synthase

GAP:

Glyceraldehyde-3-phosphate

GGPP:

Geranyl geranyl diphosphate

ggps:

Geranylgeranyl diphosphate synthase

hds:

1-Hydroxy-2-methyl-2-(E)-butenyl-4-diphosphate synthase

hdr:

1-Hydroxy-2-methyl-2-(E)-butenyl-4-diphosphate reductase

E HMBPP:

(E)-4-hydroxy-3-methylbut-2-enyl pyrophosphate

hmgr:

3-Hydroxy-3-methyl glutaryl coenzyme A reductase

hmgs:

3-Hydroxy-3-methyl glutaryl coenzyme A synthase

Ipp:

Isopentenyl diphosphate

Isph:

1-Hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase

MEP:

2-C-methyl-d-erythritol-4-phosphate

MVA:

Mevalonic acid

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Acknowledgements

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.

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Authors and Affiliations

  1. Faculty of Biology and Environmental Protection, University of Silesia in Katowice, Katowice, Poland

    Rakesh Kumar Sinha

  2. Department of Biophysics and Biochemistry of Plants, Institute of Plant Molecular Biology, Biology Centre of the ASCR, České Budějovice, Czechia

    Rakesh Kumar Sinha

  3. Department of Genetics and Plant Breeding, IGKV, Raipur, 492012, India

    Shiv Narayan Sharma & Jenu Zha

  4. Agricultural and Agri-Food Canada, Lethbridge, Canada

    Shiv S. Verma

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  1. Rakesh Kumar Sinha
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Correspondence to Rakesh Kumar Sinha.

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Communicated by J. Gao.

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Sinha, R.K., Sharma, S.N., Verma, S.S. et al. Effects of lovastin, fosmidomycin and methyl jasmonate on andrographolide biosynthesis in the Andrographis paniculata. Acta Physiol Plant 40, 165 (2018). https://doi.org/10.1007/s11738-018-2746-0

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