Abstract

Podophyllum hexandrum is the major source of podophyllotoxin (PTOX), a highly bioactive lignan of great pharmacological importance with anti-cancerous activities. The industrial demand of PTOX relies on the highly endangered natural resources only. It is therefore, desirable to elucidate global molecular processes and identify key genes for enhancing PTOX biosynthesis by overexpressing the targeted candidates. Transcriptome of leaf, rhizome, and stalk was generated to analyse the spatial regulation of PTOX biosynthesis in genetically diverse genotypes. Overall, 198 million high-quality paired-end reads were assembled into 85,531 transcripts. In addition, 32,341 transcripts were assigned gene ontologies with 6570 hits in distinct pathways and 15,886 transcription factors representing 70 families. Interestingly, comparative expression analyses revealed that 12 of 31 genes of PTOX biosynthesis were upregulated in rhizome. However, shikimate and phenylalanine pathways that generate PTOX precursors were abundantly upregulated in leaves. Thus, a further insight on the inducers of these genes can be extended to enrich the aerial tissues for downstream pathway through genetic manipulations. Additionally, higher expression of transcription factors WRKY, MYB, bZIP, bHLH, and AP2, transporters ABCB and ABCC, UGTs, CYP450s, and jasmonate pathway in rhizome supported the secondary metabolism. The comprehensive genomic resource created during this study will provide deeper understanding of lignan biosynthesis and its regulation. This will further enable selection of the elite genotypes and potential genes that can be directed to enhance PTOX production and yield at an industrial scale.

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