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

Area of Science:

• Plant biochemistry
• Genomics
• Metabolomics

Background:

• Extensive multi-omics data for camptothecin (CPT)-producing plants exist, but a unified database for studying CPT biosynthesis is lacking.
• Understanding the biological mechanisms of CPT biosynthesis is crucial for developing CPT-derived drugs.

Purpose of the Study:

• To construct DIMORPH, a comprehensive database integrating multi-omics data for CPT-producing plants.
• To facilitate the understanding of CPT biosynthetic pathways and identify key enzymes involved in CPT production.

Main Methods:

• Consolidated genomic, transcriptomic, and metabolic data from Camptotheca acuminata, Ophiorrhiza pumila, and Nothapodytes nimmoniana.
• Integrated functional annotation, synteny, and co-expression analyses.
• Utilized structural comparison and mutagenesis to identify key residues in CPT hydroxylases.

Main Results:

• Developed DIMORPH (Database Integrated Multiple Omics Resources for CPT-Producing Herbs).
• Identified a novel CPT 10-hydroxylase (CPT10H), CYP81BQ24, in C. acuminata.
• Determined ten key amino acid residues responsible for regio-selectivity in CPT hydroxylases (CPTHs) and engineered a high-efficiency CPT10H mutant.

Conclusions:

• DIMORPH provides a valuable resource for elucidating CPT biosynthetic pathways.
• The identification and characterization of CPT10H and key residues advance the understanding of CPT metabolism.
• This work supports the production of CPT and the development of CPT-derived pharmaceuticals.