DIMORPH: an integrated multi-omics resource for camptothecin-producing plants.

Over the past decade, extensive multi-omics data of camptothecin (CPT)-producing plants have been generated, resulting in a wealth of genomic resources. However, to date, no available database supports utilization for understanding biological mechanisms of CPT biosynthesis. In this study, we constructed DIMORPH ( https://www.dimorph.cn:9000 .), a Database Integrated Multiple Omics Resources for CPT-Producing Herbs. The database consolidated genomic, transcriptomic, and metabolic data of the three representative CPT-producing plants including Camptotheca acuminata, Ophiorrhiza pumila and Nothapodytes nimmoniana, and integrated functional annotation, synteny, and co-expression analytical results. Utilizing DIMORPH, a new CPT 10-hydroxylase (CPT10H), CYP81BQ24, was identified in C. acuminata. Structural comparison between CYP81BQ24 and CYP81BQ23 (CPT 11 hydroxylase), combined with fragment substitution mutagenesis, revealed ten key amino acid residues determined the regio-selectivity of CPT hydroxylases (CPTHs) at C-10 and C-11 position. Additionally, a high-efficiency CPT10H mutant was obtained through site-directed mutagenesis guided by sequence alignment and structural prediction of 17 CYP450 hydroxylases. Therefore, the comprehensive database focused on CPT will be helpful to the elucidation of CPT biosynthetic pathway and production of CPT-derived drugs.