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Biomedical subjects

Xiaoguang Lei

Publications and source records attributed to Xiaoguang Lei.

3 recordsLinked to original sources

Strigolactones constrain rice drought acclimation by suppressing ROS scavenging through the D53-OsWRKY31-ZFP36 module.

Strigolactones (SLs) are a class of plant hormones essential for tiller development and yield under diverse environmental conditions. Drought is a major limiting factor for rice yields. Although SLs contribute to drought resistance, mechanisms and practical applications of SL pathway in drought acclimation of rice remain poorly understood. Our study shows that short-term dehydration represses SL biosynthesis in rice roots. Genetic assays indicate that disruption of SL biosynthesis or signaling elevates rice drought resistance, whereas SL signaling activation or supplementation with the SL analog GR244DO impairs drought resistance. SLs negatively regulate drought acclimation by promoting degradation of the repressor protein DWARF53 (D53). D53 interacts with the transcription factor OsWRKY31 via its N-terminal domain and suppresses the protein level of OsWRKY31, which binds to and represses transcription of the ZFP36 promoter. ZFP36 encodes a zinc-finger transcription factor that promotes H2O2 scavenging to sustain reactive oxygen species (ROS) homeostasis during drought stress. Notably, the drought-resistant upland rice variety IRAT109 exhibits lower SL levels in root exudates than the lowland rice variety Nipponbare (NP). Genome editing of key components in SL pathway enhances drought resistance in NP, Huazhan (HZ), and IRAT109. The agronomic potential of tuning SL biosynthesis is further supported by the elite D17/HTD1 allele, which weakens SL biosynthesis and improves drought resistance and grain yield in Nekken 2 (NK2) under field conditions. These findings uncover a key mechanism underlying SL-repressed drought acclimation in rice and provide an effective strategy to improve drought resistance in diverse rice varieties amid ongoing climate change.

D53

Recent discovery of new enzymes in plant natural product biosynthesis.

Plants are a vast reservoir of natural products with diverse structural scaffolds, making them an invaluable source for discovering novel enzymes that catalyze unique and evolutionarily specialized metabolic transformations in biosynthetic pathways. Rapid advances in genomics, metabolomics, protein structure prediction, and heterologous pathway reconstruction have enabled the identification of numerous cryptic biosynthetic enzymes responsible for key scaffold-forming and tailoring reactions in metabolism. Particularly notable are the discoveries of plant-derived enzymes that catalyze challenging chemical transformations, including oxidative carbon-carbon bond rearrangements, atypical cycloadditions, radical-mediated coupling reactions, and iterative scaffold remodeling. This review summarizes major advances in enzyme discovery in plant natural product biosynthesis in recent years, focusing on emerging catalytic mechanisms, strategies for elucidating pathways, and evolutionary relationships, and highlights their implications for synthetic biology, metabolic engineering, and the sustainable production of valuable natural products.

Biological Products

Complete biosynthesis of the anticancer cephalotaxinone and homoerythratine.

Cephalotaxine-type and homoerythrina-type alkaloids are structurally unique and biologically important natural products isolated from endangered species that belong to the genus Cephalotaxus. Among them, homoharringtonine (HHT [1]) is a marketed drug used to treat leukemia. However, the scalable production of HHT is significantly hindered by limited natural resources. Despite intensive investigation over half a century, the complete biosynthetic pathways of these alkaloids remain unknown. Here, we applied a comprehensive multi-omics analysis and used a set of chemically synthesized standard compounds to identify the missing enzymes required for the biosynthesis of cephalotaxinone and homoerythratine. We also uncovered a rare case of divergent oxidation catalyzed by two highly homologous cytochrome P450 enzymes, CfCYP2 and CfCYP3, in the biosynthesis of two structurally distinct alkaloids. We further identified the key residues that significantly affect the divergent oxidation outcomes and ultimately reconstituted the complete biosynthetic pathways for producing these two alkaloids in N. benthamiana.

Cephalotaxus