Biology subjects

Cho, K. H.

Publications and source records attributed to Cho, K. H..

5 recordsLinked to original sources

bioRxiv2026

Aldoximes serve as auxin precursors and repress phenylpropanoid metabolism in tomato

Aldoximes are amino acid-derived metabolites that serve as precursors of auxins and modulate phenylpropanoid production in Arabidopsis. However, the enzymes responsible for aldoxime production in Solanaceae remain unknown. Here, we report the identification of aldoxime-producing enzymes in tomato (Solanum lycopersicum) and examine how altered aldoxime production affects auxin production and phenylpropanoid metabolism. Through homology-based analysis, we identified five putative CYP79 homologs in tomato, among which SlCYP79DB32 and SlCYP79DB52 exhibited aldoxime-producing activity toward multiple amino acids, including phenylalanine and tryptophan. SlCYP79DB32 and SlCYP79DB52 converted phenylalanine into phenylacetaldoxime (PAOx), whereas only SlCYP79DB52 converted tryptophan into indole-3-acetaldoxime (IAOx). Stable isotope-labeled feeding experiments revealed that IAOx and PAOx can be converted to the auxins indole-3-acetic acid (IAA) and phenylacetic acid (PAA), respectively. Consistently, tomato plants engineered to overproduce IAOx and PAOx accumulated elevated levels of IAA and PAA. These plants also accumulated lower levels of phenylpropanoids. In Brassicaceae plants such as Arabidopsis and Camelina, aldoxime accumulation represses phenylpropanoid production by promoting degradation of phenylalanine ammonia-lyase (PAL). However, aldoxime accumulation did not reduce PAL activity in tomato, suggesting an alternative mechanism in this species. Transcriptome analysis revealed extensive transcriptional reprogramming in aldoxime-overaccumulating tomato plants, including upregulation of stress- and defense-related genes. Despite the observed reduction in phenylpropanoid levels, transcript levels of most phenylpropanoid biosynthetic genes were not decreased, suggesting possible post-transcriptional regulation of this repression. Together, our findings demonstrate that aldoximes can serve as intermediates in auxin biosynthesis in tomato and reveal that aldoxime-mediated repression of phenylpropanoid metabolism extends beyond Brassicaceae.

plant biology↗

bioRxiv2025

Biosynthesis and Physiological Significance of Organ-Specific Flavonol Glycosides in Solanaceae

Flavonols are subclasses of flavonoids, with hundreds of structures identified in plants. This chemical diversity primarily arises from glycosylation, where sugars are selectively added to the flavonol backbone. While flavonol profiles vary across species and organs, the evolutionary forces shaping this chemodiversity and the physiological significance of specific glycosides remain a mystery. Here, we reveal that finely tuned transcriptional regulation and the sugar selectivity of glycosyltransferases drive the formation of distinct organ specific flavonol profiles and a specific flavonol is necessary for male fertility. In Solanaceae pollen, two flavonol glycosides, K2 (kaempferol 3-O-glucosyl(1 [->] 2)galactoside) and Q2 (quercetin 3-O-glucosyl(1 [->] 2)galactoside), are exclusively accumulated. K2 is evolutionarily conserved, while Q2 was lost over time. Consistently, K2 is essential for male fertility, whereas Q2 and aglycones fail to rescue fertility defects. These findings suggest that individual flavonol glycosides have distinct physiological roles, either actively maintained or discarded through evolutionary selection.

plant biology↗

bioRxiv2024

Generative AI-assisted Virtual Screening Pipeline for Generalizable and Efficient Drug Repurposing

Drug repurposing presents a valuable strategy to expedite drug discovery by identifying new therapeutic uses for existing compounds, especially for diseases with limited treatment options. We propose a Generative AI-assisted Virtual Screening Pipeline that combines generative modeling, binding pocket prediction, and similarity-based searches within drug databases to achieve a generalizable and efficient approach to drug repurposing. Our pipeline enables blind screening of any protein target without requiring prior structural or functional knowledge, allowing it to adapt to a wide range of diseases, including emerging health threats and novel targets where information is scarce. By rapidly generating potential ligands and efficiently identifying and ranking drug candidates, our approach accelerates the drug discovery process, broadening the scope and impact of repurposing efforts and offering new possibilities for therapeutic development. Detailed results and implementation can be accessed at https://github.com/HySonLab/DrugPipe.

bioinformatics↗

bioRxiv2024

Systematic Multi-Omics Investigation of Androgen Receptor Driven Gene Expression and Epigenetics changes in Prostate Cancer

Background: Prostate cancer, a common malignancy, is driven by androgen receptor (AR) signaling. Understanding the function of AR signaling is critical for prostate cancer research. Methods: We performed multi-omics data analysis for the AR+, androgen-sensitive LNCaP cell line, focusing on gene expression (RNAseq), chromatin accessibility (ATACseq), and transcription factor binding (ChIPseq). High-quality datasets were curated from public repositories and processed using state-of-the-art bioinformatics tools. Results: Our analysis identified 1004 up-regulated and 707 down-regulated genes in response to androgen deprivation therapy (ADT) which diminished AR signaling activity. Gene-set enrichment analysis revealed that AR signaling influences pathways related to neuron differentiation, cell adhesion, P53 signaling, and inflammation. ATACseq and ChIPseq data demonstrated that as a transcription factor, AR primarily binds to distal enhancers, influencing chromatin modifications without affecting proximal promoter regions. In addition, the AR-induced genes maintained higher active chromatin states than AR-inhibited genes, even under ADT conditions. Furthermore, ADT did not directly induce neuroendocrine differentiation in LNCaP cells, suggesting a complex mechanism behind neuroendocrine prostate cancer development. In addition, a publicly available online application LNCaP-ADT (https://pcatools.shinyapps.io/shinyADT/) was launched for users to visualize and browse data generated by this study. Conclusion: This study provides a comprehensive multi-omics dataset, elucidating the role of AR signaling in prostate cancer at the transcriptomic and epigenomic levels. The reprocessed data is publicly available, offering a valuable resource for future prostate cancer research.

cancer biology↗

bioRxiv2023

Altered methionine metabolism impacts phenylpropanoid production and plant development in Arabidopsis thaliana

Phenylpropanoids are specialized metabolites derived from phenylalanine. Glucosinolates are defense compounds derived mainly from methionine and tryptophan in Arabidopsis. It was previously shown that the phenylpropanoid pathway and glucosinolate production are metabolically linked. The accumulation of indole-3-acetaldoxime (IAOx), the precursor of tryptophan-derived glucosinolates, represses phenylpropanoid biosynthesis through accelerated degradation of phenylalanine-ammonia lyase (PAL). As PAL functions at the entry point of the phenylpropanoid pathway which produces indispensable specialized metabolites such as lignin, aldoxime-mediated phenylpropanoid repression is detrimental to plant survival. Although methionine-derived glucosinolates in Arabidopsis are abundant, any impact of aliphatic aldoximes (AAOx) derived from aliphatic amino acids such as methionine on phenylpropanoid production remains unclear. Here, we investigate the impact of AAOx accumulation on phenylpropanoid production using Arabidopsis aldoxime mutants, ref2 and ref5. REF2 and REF5 metabolize aldoximes to respective nitrile oxides redundantly, but with different substrate specificities. ref2 and ref5 mutants have decreased phenylpropanoid contents due to the accumulation of aldoximes. As REF2 and REF5 have high substrate specificity toward AAOx and IAOx respectively, it was assumed that ref2 accumulates AAOx, not IAOx. Our study indicates that ref2 accumulates both AAOx and IAOx. Removing IAOx partially restored phenylpropanoid production in ref2, but not to the wild-type level. However, when AAOx biosynthesis was silenced, phenylpropanoid production and PAL activity in ref2 were completely restored, suggesting an inhibitory effect of AAOx on phenylpropanoid production. Further feeding studies revealed that the abnormal growth phenotype commonly observed in Arabidopsis mutants lacking AAOx production is a consequence of methionine accumulation. Significance StatementAliphatic aldoximes are precursors of various specialized metabolites including defense compounds. This study reveals that aliphatic aldoximes repress phenylpropanoid production and that altered methionine metabolism affects plant growth and development. As phenylpropanoids include vital metabolites such as lignin, a major sink of fixed carbon, this metabolic link may contribute to available resource allocation during defense.

plant biology↗