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Short-chain dehydrogenase/reductase, PsDeHase, from opium poppy: putative involvement in papaverine biosynthesis

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Abstract

Benzylisoquinoline alkaloids (BIAs) are medicinal compounds that are the vital constituents of several pharmaceutical preparations, including vasodilator with papaverine. Though intermediate steps and associated enzymes involved in the biosynthesis of key BIAs of opium poppy have been characterized, very limited information is available for the biosynthesis of papaverine. Through various studies, two metabolic routes utilizing (S)-norcoclaurine as substrate for the biosynthesis of papaverine have been suggested. These two controversial pathways for papaverine biosynthesis (NH and NCH3) include a short-chain dehydrogenase/reductase (SDR) that catalyzes dehydrogenation of tetrahydropapaverine to papaverine. In this work, we have identified and functionally characterized one SDR, PsDeHase, which might participate in the dehydrogenation in the papaverine biosynthesis. The expression analysis and metabolite profiling suggested a correlation between transcript and papaverine content. The PsDeHase expressed abundantly in stem and shared homology with reductases involved in the secondary metabolism. In silico investigation predicted tetrahydropapaverine as the possible substrate that formed a stable complex with PsDeHase. Repression of PsDeHase transcripts in opium poppy plants exposed to VIGS treatment led to a comparable decrease in the accumulation of papaverine.

Key message

Using in silico and Virus-Induced Gene Silencing approaches, we demonstrate that PsDeHase, a Short-chain dehydrogenase/reductase, is putatively involved in papaverine biosynthesis in opium poppy.

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Acknowledgements

The authors are thankful to the Council of Scientific and Industrial Research, New Delhi, Govt. of India, for providing the financial support to carry out this work under Network project (BSC-107). PA, SP as well as RK acknowledge Department of Biotechnology, Government of India and University Grants Commission (UGC) for Senior and Junior Research Fellowships. CSIR-NBRI No.: MS/2020/09/02

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PA, SP, SS and PKT designed the research. PA and RK performed the experiments. YVD carried out the bioinformatics analysis. PA and PKT wrote the paper.

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Correspondence to Prabodh Kumar Trivedi.

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Authors declare that they have no competing interests. All authors have read and approved the final manuscript.

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Communicated by Manoj Prasad.

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Agarwal, P., Pathak, S., Kumar, R.S. et al. Short-chain dehydrogenase/reductase, PsDeHase, from opium poppy: putative involvement in papaverine biosynthesis. Plant Cell Tiss Organ Cult 143, 431–440 (2020). https://doi.org/10.1007/s11240-020-01930-2

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