A5015800814- Enzyme Catalysis and Immobilization
- Metal-Catalyzed Oxygenation Mechanisms
- Plant biochemistry and biosynthesis
- Microbial Natural Products and Biosynthesis
- Antifungal resistance and susceptibility
- Microbial Metabolic Engineering and Bioproduction
- Carbohydrate Chemistry and Synthesis
- Computational Drug Discovery Methods
- Cyclopropane Reaction Mechanisms
- Asymmetric Synthesis and Catalysis
- S100 Proteins and Annexins
- Nanoparticle-Based Drug Delivery
- Immune cells in cancer
- Innovative Microfluidic and Catalytic Techniques Innovation
- Chemical Synthesis and Analysis
- Synthetic Organic Chemistry Methods
- Nanomaterials for catalytic reactions
- Amino Acid Enzymes and Metabolism
- Ocular Oncology and Treatments
- Nanoplatforms for cancer theranostics
- Biological Stains and Phytochemicals
- Retinal and Optic Conditions
- Pancreatic function and diabetes
- Protein Degradation and Inhibitors
- Traumatic Brain Injury and Neurovascular Disturbances
Shanghai University of Traditional Chinese Medicine
2021-2024
Affiliated Eye Hospital of Wenzhou Medical College
2023-2024
Wenzhou Medical University
2023-2024
Center for Excellence in Molecular Plant Sciences
2021
University of Chinese Academy of Sciences
2021
Zhejiang University
2016-2019
Hangzhou Xixi hospital
2019
Chinese Academy of Sciences
2019
Shanghai Institute of Organic Chemistry
2019
Enzymatic stereodivergent synthesis to access all possible product stereoisomers bearing multiple stereocenters is relatively undeveloped, although enzymes are being increasingly used in both academic and industrial areas. When two thus four stereoisomeric products involved, obtaining enzyme mutants for individually accessing would be ideal. Although significant success has been achieved directed evolution of general, engineering one into highly stereocomplementary variants the full...
Abstract Engineering artificial enzymes with high activity and catalytic mechanism different from naturally occurring is a challenge in protein design. For example, many attempts have been made to obtain active hydrolases by introducing Ser → Cys exchange at the respective triads, but this generally induced breakdown of activity. We now report that long-standing dogma no longer pertains, provided additional mutations are introduced directed evolution. By employing Candida antarctica lipase B...
The 2-oxoglutarate (2OG)-dependent non-heme enzyme FtmOx1 catalyzes the endoperoxide biosynthesis of verruculogen. Although several mechanistic studies have been carried out, catalytic mechanism is not well determined owing to lack a reliable complex structure with fumitremorgin B. Herein we provide X-ray crystal ternary FtmOx1⋅2OG⋅fumitremorgin B at resolution 1.22 Å. Our structures show that binding induces significant compression active pocket and Y68 in close proximity C26 substrate....
Abstract Uveal melanoma (UM) is the most frequent primary intraocular malignancy with high metastatic potential and poor prognosis. Macrophages represent one of abundant infiltrating immune cells diverse functions in cancers. However, cellular heterogeneity functional diversity macrophages UM remain largely unexplored. In this study, we analyzed 63,264 single-cell transcriptomes from 11 patients identified four transcriptionally distinct macrophage subsets (termed MΦ-C1 to MΦ-C4). Among...
Being the rate-limiting enzyme within serine biosynthesis pathway, phosphoglycerate dehydrogenase (PHGDH) is abnormally overexpressed in numerous malignant tumor cells and a promising target for cancer treatment. Here, we report series of novel PHGDH inhibitors using focused compound screening structural optimization approach. The lead D8 displayed good enzymatic inhibitory activity (IC50 = 2.8 ± 0.1 μM), high binding affinity (Kd 2.33 sensitivity to cell lines with gene amplification or...
Metal-free enantiocomplementary hydrolytic dynamic kinetic resolution of Morita–Baylis–Hillman (MBH) acetates was developed using triethylamine (TEA) as a racemization catalyst and wild-type or engineered lipase B from Candida antarctica (CALB) stereoselectivity-determining catalyst, leading to chiral MBH alcohols with tailor-made R S configurations on an optional basis. In the TEA-WT CALB catalysis system, WT displays excellent enantioselectivity for series tested (up 96% ee 98%...
Abstract Candida antarctica lipase B (CALB) is one of the most extensively used biocatalysts in both academia and industry exhibits remarkable ( R )‐enantioselectivity for various chiral sec ‐alcohols. Considering significance tailor‐made stereoselectivity organic synthesis, a discovery enantiocomplementary mutants with high )‐ S )‐selectivity valuable highly desired. Herein, we report efficient directed evolution strategy, using only 4 representative amino acids, namely, alanine (A),...
Abstract The 2‐oxoglutarate (2OG)‐dependent non‐heme enzyme FtmOx1 catalyzes the endoperoxide biosynthesis of verruculogen. Although several mechanistic studies have been carried out, catalytic mechanism is not well determined owing to lack a reliable complex structure with fumitremorgin B. Herein we provide X‐ray crystal ternary FtmOx1⋅2OG⋅fumitremorgin B at resolution 1.22 Å. Our structures show that binding induces significant compression active pocket and Y68 in close proximity C26...
Single mutation F432I/L or L435A/G remarkably reversed the (−)-selectivity of WT CHMO<sub>Acineto</sub>.
In nature, cyclopropylcarbinyl cation is often involved in cationic cascade reactions catalyzed by natural enzymes to produce a great number of structurally diverse substances. However, mimicking this process with artificial organic catalysts remains daunting challenge synthetic chemistry. We report small molecule-catalyzed asymmetric rearrangement cations, leading series chiral homoallylic sulfide products good excellent yields and enantioselectivities (up 99% enantiomeric excess). the...
The 3C-like protease (3CL pro ) is a crucial target in anti-Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) drug design. Herein, we performed high-throughput synthesis of catechol derivatives from the bioactive catechol-terminal alkyne scaffold A4 , by using modular click chemistry. Subsequently, conducted two rounds SARS-CoV-2 3CL inhibition screening and selected seven compounds for further efficacy validation. Compound P1-E11 had potent inhibitory effects toward (IC 50 = 2.54...
Abstract Enzymatic Baeyer‐Villiger oxidation provides a promising green route utilizing molecular oxygen as the oxidant to produce chiral lactones. Wild‐type (WT) CHMO Acineto leads enantioselectivity up 99 % ee ( S ) in synthesis of substituted ϵ‐caprolactones. To reverse inherent enantiopreference toward an array cyclohexanones with various chain length, we herein reshaped binding pocket minimal number mutations by rational design strategy combining “size‐probes” silico study, which...
Abstract The high‐resolution X‐ray crystal structure of the ternary complex FtmOx1 ⋅ 2OG fumitremorgin B and catalytic mechanism were recently reported by us (DOI 10.1002/anie.202112063 ). In their Correspondence, Zhang, Costello, Liu et al. criticize our work in several aspects. Herein, we address these questions one one. These structural clarifications new computational results further support CarC‐like mechanistic model.