A5028839532- Radical Photochemical Reactions
- Enzyme Catalysis and Immobilization
- Sulfur-Based Synthesis Techniques
- Microbial Natural Products and Biosynthesis
- Biochemical Analysis and Sensing Techniques
- Cellular transport and secretion
- Catalytic C–H Functionalization Methods
- Plant biochemistry and biosynthesis
- Metal-Catalyzed Oxygenation Mechanisms
- Microbial Metabolites in Food Biotechnology
- Microbial Metabolic Engineering and Bioproduction
- Glycosylation and Glycoproteins Research
- Click Chemistry and Applications
- Crystallization and Solubility Studies
- RNA and protein synthesis mechanisms
- X-ray Diffraction in Crystallography
- Plant Gene Expression Analysis
- Lipid Membrane Structure and Behavior
- Plant-Microbe Interactions and Immunity
- Enzyme Structure and Function
- Nanoplatforms for cancer theranostics
- Enzyme Production and Characterization
- Porphyrin and Phthalocyanine Chemistry
- Autophagy in Disease and Therapy
- Tryptophan and brain disorders
Jiangnan University
2018-2025
Wuxi Institute of Technology
2019-2020
Max Planck Institute of Biochemistry
2011-2019
Leibniz-Forschungsinstitut für Molekulare Pharmakologie
2013
Freie Universität Berlin
2010-2012
Fujian Institute of Research on the Structure of Matter
2006
Chinese Academy of Sciences
2006
Chinese Academy of Social Sciences
2006
Members of the Bin/amphiphysin/Rvs (BAR) domain protein superfamily are involved in membrane remodeling various cellular pathways ranging from endocytic vesicle and T-tubule formation to cell migration neuromorphogenesis. Membrane curvature induction stabilization encoded within BAR or Fer-CIP4 homology-BAR (F-BAR) domains, α-helical coiled coils that dimerize into membrane-binding modules. BAR/F-BAR proteins often contain an SH3 domain, which recruits binding partners such as oligomeric...
Abstract Autophagosomes are double-membrane vesicles that sequester cytoplasmic material for lysosomal degradation. Their biogenesis is initiated by recruitment of Atg9-vesicles to the phagophore assembly site. This process depends on regulated activation Atg1–kinase complex. However, underlying molecular mechanism remains unclear. Here we reconstitute this early step in autophagy from purified components vitro . We find its subcomplexes, complex becomes activated, enabling it recruit and...
Diaryl ketones are important building blocks for synthesizing pharmaceuticals and generally regarded as "difficult-to-reduce" due to the large steric hindrance of their two bulky aromatic side chains. Alcohol dehydrogenase from Kluyveromyces polyspora (KpADH) has been identified a robust biocatalyst its high conversion diaryl ketone substrate (4-chlorophenyl)(pyridine-2-yl)ketone (CPMK) with moderate R-selectivity 82% ee. To modulate stereoselectivity KpADH, "polarity scanning" strategy was...
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Abstract Plant-derived alkaloids are an important class of pharmaceuticals. However, they still rely on phytoextraction to meet their diverse market demands. Since multistep biocatalytic cascades have begun revolutionize the manufacture natural or unnatural products, address synthetic challenges alkaloids, herein we establish artificially concise four-enzyme cascade with avoiding plant-derived P450 modification for synthesizing phenethylisoquinoline (PEIAs) after enzyme discovery and...
Cercosporin was developed as a green and efficient organophotocatalyst for wide range of selective oxidations with reactive oxygen species.
Owing to zero-calorie and advanced organoleptic properties similar sucrose, the plant-derived rebaudioside M (Reb M) has been considered as a next generation sweetener. However, low content of Reb in Stevia rebaudiana Bertoni enzymatic activity UGT76G1, which is an uridine diphosphate glucose (UDPG)-dependent glycosyltransferase with ability glycosylate D D) produce through formation β-1,3 glycosidic bond, restrict its commercial usage. To improve catalytic variant UGT76G1-T284S/M88L/L200A...
New-to-nature biocatalysis in organic synthesis has recently emerged as a green and powerful strategy for the preparation of valuable chiral products, among which oxygen-containing benzo-fused heterocycles are important structural motifs pharmaceutical industry. However, asymmetric these compounds through radical-mediated methods is challenging. Herein, novel photoenzymatic developed to realize efficient enantioselective structure-guided engineering flavin-dependent 'ene'-reductase GluER. It...
An atypical nonheme iron-dependent dioxygenase BTG13 with a rare iron coordination of four histidine residues and carboxylated-lysine (Kcx) was recently reported to catalyze the C4a–C10 bond cleavage anthraquinone. However, reaction mechanism remains elusive. Herein, detailed is studied using molecular dynamics simulations density functional theory calculations. The comprehensive mechanistic study shows that most favorable pathway for C–C anthraquinone involves two unusual steps: (1)...
Enzyme thermostability is vital for prolonged reactions and reusability. Extremozymes, known their high thermal stability, have gained biocatalysis prominence. Extremozymes evolve under extreme conditions, possibly becoming extinct during the evolutionary process of adapting to current environment. Fortunately, ancestral enzyme sequence reconstruction could deduce existing enzymes through computer algorithms. Here, we designed an sequence-structure-molecule dynamics (ASSMD) strategy unveil...
The strength of synaptic inhibition can be controlled by the stability and endocytosis surface GABA A receptors (GABA Rs), but receptor dynamics that underpin R recruitment to dendritic endocytic zones (EZs) have not been investigated. Stabilization Rs at EZs is likely regulated interactions with clathrin-adaptor AP2, molecular determinants these associations remain poorly understood. Moreover, although downmodulation plays a key role in pathological disinhibition conditions such as ischemia...
A d-carbamoylase NiHyuC from Nitratireductor indicus was identified with high catalytic activity toward N-carbamoyl-d-tryptophan (3a). To further enhance its efficiency, both random mutagenesis and structure-guided evolution were performed. Variant M4 (D187N/A200N/S207A/R211G) showed a 43-fold increase in efficiency (kcat/Km = 1135.0 min–1 mM–1) 21-fold reduction Km value (0.4 mM) compared WT. Crystal structures of beneficial variants resolved to clarify the evolutionary changes underlying...
Sunlight along with cercosporin, produced by a new endophytic fungus, catalyzes the direct arylation of (het)arenes photoredox process.
Nitrogen-containing heterocycles are especially considered "privileged" structural scaffolds for the development of new drugs. However, traditional methods organic synthesis mainly based on thermal cycloaddition reaction; thus, exploration strategies rapid assembly N-heterocycles under mild conditions is highly desirable. Here, we developed a method that visible light along with 1 mol % cercosporin, which one perylenequinonoid pigments excellent properties photosensitization and can be...
The narrow substrate scope limits the wide industrial application of enzymes. Here, we successfully broadened a nitrile hydratase (NHase) through mutation two tunnel entrance residues based on rational calculation. Two variants, with increased specific activity, especially toward bulky substrates, were obtained. Crystal structure analysis revealed that mutations led to expansion entrance, which might be conducive entry. More importantly, molecular dynamics simulations illustrated introduced...
Abstract The construction of structural complexity and diversity natural products is crucial for drug discovery development. To overcome high dark toxicity poor photostability photosensitizer perylenequinones (PQs) photodynamic therapy, herein, we aim to introduce the biosynthesize desired unnatural PQs in fungus Cercospora through synthetic biology‐based strategy. Thus, first elucidate intricate biosynthetic pathways class B reveal how branching enzymes create their from a common ancestor....
The successful biomimetic or chemoenzymatic synthesis of target natural products (NPs) and their derivatives relies on enzyme discovery. Herein, we discover a fungal P450 BTG5 that can catalyze the formation bicyclo[3.2.2]nonane structure through an unusual two-step mechanism dimerization cyclization in biosynthesis beticolin 1, whose skeleton connects anthraquinone moiety xanthone moiety. Further investigation reveals BTG5-T318 not only determines substrate selectivity but also alters...
Steviol glycosides (SGs) are highly valued for their sweetness, safety, and zero calories, but bitter taste low solubility limit application. Modifying glycosyl units is a promising strategy to improve sensory qualities. In this study, we identified the enzyme UGT94E13 through phylogenetic analysis screening, which catalyzes glycosylation of rebaudioside M2 (Reb M2) at C-13 position, producing novel β-1,6-O-glycosylated product M9 M9). Subsequently, catalytic activity toward Reb was enhanced...