From genomics to metabolomics: Deciphering sanguinarine biosynthesis in Dicranostigma leptopodum.

ABSTRACT

Dicranostigma leptopodum (Maxim) Fedde (DLF) is a renowned medicinal plant in China, known to be rich in alkaloids. However, the unavailability of a reference genome has impeded investigation into its plant metabolism and genetic breeding potential. Here we present a high-quality chromosomal-level genome assembly for DLF, derived using a combination of Nanopore long-read sequencing, Illumina short-read sequencing and Hi-C technologies. Our assembly genome spans a size of 621.81 Mb with an impressive contig N50 of 93.04 Mb. We show that the species-specific whole-genome duplication (WGD) of DLF and Papaver somniferum corresponded to two rounds of WGDs of Papaver setigerum. Furthermore, we integrated comprehensive homology searching, gene family analyses and construction of a gene-to-metabolite network. These efforts led to the discovery of co-expressed transcription factors, including NAC and bZIP, alongside sanguinarine (SAN) pathway genes CYP719 (CFS and SPS). Notably, we identified P6H as a promising gene for enhancing SAN production. By providing the first reference genome for Dicranostigma, our study confirms the genomic underpinning of SAN biosynthesis and establishes a foundation for advancing functional genomic research on Papaveraceae species. Our findings underscore the pivotal role of high-quality genome assemblies in elucidating genetic variations underlying the evolutionary origin of secondary metabolites.