Piperaceae plants have been traditionally used to alleviate cancer-like symptoms.1 Piperlongumine is a major bioactive alkaloid produced by Piper species, which demonstrated selective in vitro and in vivo cytotoxicity against various human cancer cell lines by triggering apoptotic and autophagic cell death2. Piperlongumine displays the same amide moiety as piperine, another piper alkaloid for which the last enzymatic step of biosynthesis is catalyzed by a BAHD enzyme.3 We have generated hypotheses that amidation of piperlongumine might be catalyzed in a similar fashion to piperine through BAHD acyltransferase-mediated catalysis. Using metabolomics, we selected P. fimbriulatum because this Piperaceae plant accumulates more piperlongumine than the fifteen other species we tested. We extracted mRNA from P. fimbrulatum and assembled its de novo transcriptome. Through a comparative analysis of transcriptomes of different species to identify homologous proteins of BAHD, we are conducting functional characterization of these proteins using agrobacterium-mediated heterologous expression in tobacco. The products of the transient expression will be analyzed by high-resolution mass spectrometry to confirm the function of the enzymes. Elucidating the entire pathway holds promise for the production of this compound and its derivatives via metabolic engineering. Compared to traditional technologies, bioengineering provides a more sustainable, less time-consuming process and ecologically favored strategies to synthesize high-value chemicals.
1. Wang, Y.-H. et al. Anticancer principles from medicinal piper ( hú jiāo) plants. Afr. J. Tradit. Complement. Altern. Med. 4, 8–16 (2014).
2. Wang, H. et al. Piperlongumine induces apoptosis and autophagy in leukemic cells through targeting the PI3K/Akt/mTOR and p38 signaling pathways. Oncol. Lett. 15, 1423–1428 (2018).
3. Schnabel, A. et al. Identification and characterization of piperine synthase from black pepper, Piper nigrum L. Commun Biol 4, 445 (2021).
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