Yao Nie

Jiangnan University

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i-10 index

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Co-Authors

Yan Xu

Jiangnan University

106

Rong Xiao

Huazhong Agricultural University

Xiaoqing Mu

Jiangnan University

Xian‐Chun Zeng

China University of Geosciences

Lunjie Wu

Jiangnan University

Xuesong Luo

Huazhong Agricultural University

Minying Chen

The First Affiliated Hospital, Sun Yat-sen University

Jie Gu

Jiangnan University

Xiaoran Jing

Jiangnan University

Xiao Qing Mu

Jiangnan University

Cooperative Institutions

Jiangnan University

107

Chinese Academy of Sciences

Sun Yat-sen University

The First Affiliated Hospital, Sun Yat-sen University

University of Chinese Academy of Sciences

Shanghai Jiao Tong University

State Key Laboratory of Food Science and Technology

Chinese Academy of Medical Sciences & Peking Union Medical College

Ministry of Agriculture and Rural Affairs

Capital Medical University

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Ancestor-originated engineering of medium-chain alcohol dehydrogenase enhances its catalytic compatibility by balancing activity, stability, and selectivity trade-offs

Molecular Catalysis (2024)

Jun Wang Lei Qin Jie Gu Lunjie Wu Man Zou

Ancestor

10.1016/j.mcat.2024.114657

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Citations (0)

Origin of the Unexpected Enantioselectivity in the Enzymatic Reductions of 5-Membered-Ring Heterocyclic Ketones Catalyzed by Candida parapsilosis Carbonyl Reductases

Catalysts (2022)

Byu Ri Sim Jie Gu Yvette Ley Shenggan Luo Yihan Liu

Candida parapsilosis carbonyl reductases (CpRCR) have been widely used for the reductive conversion of ketone precursors and chiral alcohol products in pharmaceutical industries. The enzymatic enantioselectivity is believed to be related to the shape complementation between the cavities in the enzymes and the substitutions of the ketone substrates. In this work, we reported an unexpected enantioselectivity in the enzyme reductions of dihydrofuran-3(2H)-one (DHF) to (S)-tetrahydrofuran-3-ol (DHF-ol, enantiomeric excess: 96.4%), while dihydrothiophen-3(2H)-one substrate (DHT) was unproductive under the same experimental conditions. To rationalize the exclusive S-configuration and the specific reactivity of DHF, we carried out molecular dynamics simulations for the reacting complexations of DHF with CpRCR, and DHT with CpRCR. Our calculations indicate that DHF preferentially binds to the small cavity near L119, F285, and W286, while the large cavity near the α1 helix was mainly occupied by solvent water molecules. Moreover, the pre-reaction state analysis suggests that the pro-S conformations were more abundant than the pro-R, in particular for DHF. This suggests that the non-polar interaction of substrate C4-C5 methylene contacting the hydrophobic side-chains of L119-F285-W286, and the polar interaction of funanyl oxygen exposing the solvent environment play important roles in the enantioselectivity and reactivity. The phylogenetic tree of CpRCR homologues implies that a variety of amino acid combinations at positions 285 and 286 were available and thereby potentially useful for redesigning enantioselective reductions of 5-membered-ring heterocyclic ketones.

Candida parapsilosis

Reactivity

10.3390/catal12101086

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Citations (5)

Reshaping Substrate-Binding Pocket of Leucine Dehydrogenase for Bidirectionally Accessing Structurally Diverse Substrates

ACS Catalysis (2022)

Tao Wu Yinmiao Wang Ningxin Zhang Dejing Yin Yan Xu

Steric hindrance modification-based pocket reshaping is an effective approach for enzyme–substrate acceptance evolution. However, previous studies were limited to using the unidirectional acceptance trait of bulky substrates as a measure of fitness. In this endeavor, we conducted steric hindrance modification-based bidirectional pocket reshaping of Exiguobacterium sibiricum leucine dehydrogenase (EsLeuDH) for elucidating the differences in the molecular mechanism of pocket steric hindrance on the adaptability between the bulky and small substrates. A site-directed mutagenesis library generated based on the specifically chosen bidirectional mutagenesis sites and building blocks enabled the substrate specificity of EsLeuDH to be extended to both the small aliphatic 1a and bulky aromatic 1h; the catalytic efficiency toward 1b–g increased by 2.5–16.3-fold. Kinetic parameter determination revealed that the increased acceptance of the mutants toward small and bulky substrates was attributed to the decreased Km and enhanced kcat values, respectively. Structure-based computational analysis provided insights into the increased acceptance in both the steric hindrance strengthening and attenuating directions, which was attributed to the reshaped pocket with a favorable attack distance and an expanded catalytical binding space, respectively. Our study elucidates the mechanism difference of pocket steric hindrance of EsLeuDH on the adaptability of different types of substrates based on the implementation of bidirectional pocket reshaping, with potential applications in the divergent substrate acceptance evolution of amino acid dehydrogenase family members and other oxidoreductases with analogous substrate-binding pocket.

10.1021/acscatal.2c04735

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Citations (39)

Semi-Rational Design of Proteus mirabilis l-Amino Acid Deaminase for Expanding Its Substrate Specificity in α-Keto Acid Synthesis from l-Amino Acids

Catalysts (2022)

Anwen Fan Ziyao Wang Haojie Qu Yao Nie Yan Xu

l-amino acid deaminases (LAADs) are flavoenzymes that catalyze the stereospecific oxidative deamination of l-amino acids into α-keto acids, which are widely used in the pharmaceutical, food, chemical, and cosmetic industries. However, the substrate specificity of available LAADs is limited, and most substrates are concentrated on several bulky or basic l-amino acids. In this study, we employed a LAAD from Proteus mirabilis (PmiLAAD) and broadened its substrate specificity using a semi-rational design strategy. Molecular docking and alanine scanning identified F96, Q278, and E417 as key residues around the substrate-binding pocket of PmiLAAD. Site-directed saturation mutagenesis identified E417 as the key site for substrate specificity expansion. Expansion of the substrate channel with mutations of E417 (E417L, E417A) improved activity toward the bulky substrate l-Trp, and mutation of E417 to basic amino acids (E417K, E417H, E417R) enhanced the universal activity toward various l-amino acid substrates. The variant PmiLAADE417K showed remarkable catalytic activity improvement on seven substrates (l-Ala, l-Asp, l-Ile, l-Leu, l-Phe, l-Trp, and l-Val). The catalytic efficiency improvement obtained by E417 mutation may be attributed to the expansion of the entrance channel and its electrostatic interactions. These PmiLAAD variants with a broadened substrate spectrum can extend the application potential of LAADs.

Oxidative deamination

Saturated mutagenesis

Deamination

Alanine

10.3390/catal12020175

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Citations (3)

A single-atom iron nanozyme reactor for α-ketoglutarate synthesis

Chemical Engineering Journal (2023)

Yun Sun Xiaoran Jing Bolong Xu Huan Liu Min Chen

Nanoreactor

Biocatalysis

Oxidative deamination

Deamination

10.1016/j.cej.2023.143269

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Citations (10)

Influence of Site-Directed Mutagenesis in Coenzyme-Binding Domain of Car-bonyl Reductase on Its Catalytic Performance for Asymmetric Reduction

CHINESE JOURNAL OF CATALYSIS (CHINESE VERSION) (2013)

Xu-Min Gong Yao Nie Yan Xu Rong Xiao G.T. Montelione

Site-directed mutagenesis

Coenzyme A

10.3724/sp.j.1088.2012.10851

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Citations (0)

Substrate-Specific Engineering of Amino Acid Dehydrogenase Superfamily for Synthesis of a Variety of Chiral Amines and Amino Acids

Catalysts (2022)

Feng Zhou Yan Xu Yao Nie Xiaoqing Mu

Amino acid dehydrogenases (AADHs) are a group of enzymes that catalyze the reversible reductive amination of keto acids with ammonia to produce chiral amino acids using either nicotinamide adenine dinucleotide (NAD+) or nicotinamide adenine dinucleotide phosphate (NADP+) as cofactors. Among them, glutamate dehydrogenase, valine dehydrogenase, leucine dehydrogenase, phenylalanine dehydrogenase, and tryptophan dehydrogenase have been classified as a superfamily of amino acid dehydrogenases (s-AADHs) by previous researchers because of their conserved structures and catalytic mechanisms. Owing to their excellent stereoselectivity, high atom economy, and low environmental impact of the reaction pathway, these enzymes have been extensively engineered to break strict substrate specificities for the synthesis of high value-added chiral compounds (chiral amino acids, chiral amines, and chiral amino alcohols). Substrate specificity engineering of s-AADHs mainly focuses on recognition engineering of the substrate side chain R group and substrate backbone carboxyl group. This review summarizes the reported studies on substrate specificity engineering of s-AADHs and reports that this superfamily of enzymes shares substrate specificity engineering hotspots (the inside of the pocket, substrate backbone carboxyl anchor sites, substrate entrance tunnel, and hinge region), which sheds light on the substrate-specific tailoring of these enzymes.

Protein Engineering

10.3390/catal12040380

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Citations (14)

Terlipressin relieves intestinal and renal injuries induced by acute mesenteric ischemia via PI3K/Akt pathway

International Journal of Medical Sciences (2020)

Zimeng Liu Han-Jin Lai Xiangdong Guan Shihong Wen Jiantong Shen

Background: To date, the effect of vasopressin on organ damages after acute mesenteric ischemia (MI) remains poorly understood.Aims: To investigate the effect of terlipressin, a selective vasopressin V1 receptor agonist, versus norepinephrine on the intestinal and renal injuries after acute MI, and to explore the underlying mechanism of terlipressin.Methods: Acute MI model was produced by clamping the superior mesenteric artery for 1 hour.Immediately after unclamping, terlipressin or norepinephrine was intravenously administered for 2 hours.Meanwhile, in vitro, RAW264.7 cells were treated with lipopolysaccharide or lipopolysaccharide+terlipressin.In addition, wortmannin was used to determine the role of phosphoinositide 3-kinase (PI3K)/ protein kinase B (Akt) pathway in the potential impacts of terlipressin.Results: MI led to severe hypotension, caused notable intestinal and renal impairments and resulted in high mortality, which were markedly improved by terlipressin or norepinephrine.Terlipressin increased mean arterial pressure, decreased intestinal epithelial cell apoptosis, inhibited the generation of M1 macrophage in intestinal and renal tissues, and hindered the release of inflammatory cytokines after MI.Moreover, in cultured macrophages, terlipressin reduced the mRNA level of specific M1 markers and the release of inflammatory cytokines caused by lipopolysaccharide challenge.Wortmannin decreased the expression of PI3K and Akt induced by terlipressin in cells and in tissues, and abolished the above protective effects conferred by terlipressin.Conclusions: Terlipressin or norepinephrine could effectively improve organ damages and mortality after acute MI.Terlipressin elevates blood pressure and inhibits intestinal epithelial apoptosis and macrophage M1 polarization via the PI3K/Akt pathway.

Terlipressin

Wortmannin

10.7150/ijms.46302

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Citations (2)

Early sedation using ciprofol for intensive care unit patients requiring mechanical ventilation: a pooled post-hoc analysis of data from phase 2 and phase 3 trials

Annals of Intensive Care (2024)

Yong-Jun Liu Lingyun Zuo Xiaoyun Li Yao Nie Chuanxi Chen

Ciprofol was approved for use in intensive care unit (ICU) patients requiring sedation during mechanical ventilation in July 2022. A pooled post-hoc analysis of phase 2 and phase 3 trials was conducted primarily to explore hypotension-free outcome in ICU patients who required mechanical ventilation and achieved the target light sedation goal at an early stage after being sedated with ciprofol or propofol.

Post-hoc analysis

Post hoc

Pain medicine

10.1186/s13613-024-01390-3

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Citations (1)

The formation and structural characteristics of melanoidins from fermenting and distilled grains of Chinese liquor (baijiu)

Food Chemistry (2022)

Shiqi Yang Wenlai Fan Yao Nie Yan Xu

Melanoidin

Distilled water

10.1016/j.foodchem.2022.135372

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Citations (12)