Omics approaches to harness daphniphyllum alkaloid diversity Benjamin Lichman 1 , Kaouthar Eljounaidi 1 , Samuel J. Smit 1 , Sandesh Swamidatta 1 , Caragh Whitehead 1 , William Davis 1 , Daphne Ezer 1 , Susana Conde 1 , Tony Larson 1 , Katherine Newling 1 , Barbara Radikowska 1 , William Unsworth 2
1 Department of Biology, University of York, UK, 2 Department of Chemistry, University of York, UK
Plants from the genus Daphniphyllum produce a variety of unique alkaloids of remarkable complexity. Over 320 Daphniphyllum alkaloids (DA) have been identified, with over 30 different carbon skeletal forms all featuring multiple fused rings and stereogenic quaternary carbon centres 1 . Reports of bioactivities in isolated compounds indicate DAs may have pharmaceutical potential 2 . In addition, enzymes and pathways capable of forming complex structures may have wider applications in biochemical syntheses. To understand the biosynthetic origins of DAs, we performed metabolomics experiments and discovered that the DA metabolism is subdivided into pathways that are under different regulatory and/or spatial controls 3 . Next, obtained a transcriptome using Nanopore and Illumina technologies to reveal gene modules and specific transcripts that correlate closely with DA subtype accumulation. We are establishing complementary yeast and Nicotiana platforms for screening enzyme candidates. This work represents the first multi-omics investigation into a neglected alkaloid class and sets the stage for the discovery of new enzymes involved in the biosynthesis of Daphniphyllum alkaloids and the engineering of synthetic biology platforms for their production.
References 1. Heathcock, C. H. (1992). Angew. Chem. Int. Ed. 31: 665–804. 2. Chattopadhyay, A. K. and Hanessian, S. (2017). Chem.Rev. 117: 4104–4146. 3. Eljounaidi et al . In preparation
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