Identification of P450 Candidates Associated with the Biosynthesis of Physalin-Class Compounds in Physalis angulata

Abstract

The Physalis genus has long been used as traditional medicine in the treatment of various diseases. Physalins, the characteristic class of compounds in this genus, are major bioactive constituents. To date, the biogenesis of physalins remains largely unknown, except for the recently established knowledge that 24-methyldesmosterol is a precursor of physalin. To identify the genes encoding P450s that are putatively involved in converting 24-methyldesmosterol to physalins, a total of 306 P450-encoding unigenes were retrieved from our recently constructed P. angulata transcriptome. Extensive phylogenetic analysis proposed 21 P450s that might participate in physalin biosynthesis. To validate the candidates, we developed a virus-induced gene silencing (VIGS) system for P. angulata, and four P450 candidates were selected for the VIGS experiments. The reduction in the transcripts of the four P450 candidates by VIGS all led to decreased levels of physalin-class compounds in the P. angulata leaves. Thus, this study provides a number of P450 candidates that are likely associated with the biosynthesis of physalin-class compounds, forming a strong basis to reveal the unknown physalin biosynthetic pathway in the future.

DeepP450: Predicting Human P450 Activities of Small Molecules by Integrating Pretrained Protein Language Model and Molecular Representation

“…PlantP450Test2 comprised 155 plant CYPs and 85 molecules, 157 CYP-substrate pairs, and 34 CYP-nonsubstrate pairs. − Figure C and D reveals that only 12% of small molecules in this set exhibit molecular similarity greater than 0.70 with TrainSet molecules, while 65% have similarity values below 0.5. Additionally, Figure E shows distinct clusters for plant and human CYPs in the t-SNE dimensionality reduction, indicating a lower degree of similarity between these groups.…”