Catalysis Science & Technology
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2020
·Vol. 10
·期 17
·5945-5952
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IF 5.721
Hongyue Wang,Ge Qu,Jun-Kuan Li,Jun-An Ma,Jinggong Guo,Yuchen Miao,Zhoutong Sun
Chiral amino alcohols are essential building blocks for the pharmaceutical industry, and are widely present in natural and synthetic bioactive compounds. Amine dehydrogenases (AmDHs) can asymmetrically reduce prochiral ketones with low-cost ammonia to chiral amines and water as by-products, using NAD(P)H as a cofactor under mild conditions, but hydroxy ketones with formation of chiral hydroxy amines have rarely been investigated. In this study, six new bacterial AmDHs derived from amino acid dehydrogenases (AADHs) were identified by data mining, and five out of the six enzymes were able to efficiently reduce 1-hydroxybutan-2-one (1a) to (S)-2-aminobutan-1-ol ((S)-2a) with 19–99% conversions and 99% ee. The five AmDHs were purified and biochemically characterized for reductive amination activity towards substrate 1a with the optimal pH at 8.5 or 9.0 and the optimal temperature at 45 °C, 50 °C or 55 °C, and provided reductive amination of a broad range of prochiral α-hydroxy ketones, and even of a model β-hydroxy ketone leading to β-hydroxy amine with 99% ee. Our study expands the toolbox of AmDHs in the synthesis of chiral amino alcohols.
研究领域:
生物化学
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合成生物学
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酶工程
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DOI
高影响因子
JOURNAL OF ORGANIC CHEMISTRY
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2019
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IF 4.745
Fei-Fei Chen,Yu-Hui Zhang,Zhi-Jun Zhang,Lei Liu,Jian-Ping Wu,Jian-He Xu,Gao-Wei Zheng
(R)-Amination mediated by (R)-specific ω-transaminases generally requires costly d-alanine in excess to obtain the desired chiral amines in high yield. Herein, a one-pot, trienzymatic cascade comprising an (R)-specific ω-transaminase, an amine dehydrogenase, and a formate dehydrogenase was developed for the economical and eco-friendly synthesis of (R)-chiral amines. Using inexpensive ammonium formate as the sole sacrificial agent, the established cascade system enabled efficient ω-transaminase-mediated (R)-amination of various ketones, with high conversions and excellent ee (>99%); water and CO2 were the only waste products.
研究领域:
生物催化
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有机合成
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酶工程
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手性化学
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DOI
PubMed
高影响因子
Frontiers in Immunology
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2021
·
IF 7.561
Zhang Weibin,Zhu Chunhua,Xiao Fangnan,Liu Xiaodong,Xie Anhua,Chen Fangman,Dong Panpan,Lin Pingdong,Zheng Chenyang,Zhang Hong,Gong Hui,Wu Yunkun
The development of effective vaccines and delivery systems in aquaculture is a long-term challenge for controlling emerging and reemerging infections. Cost-efficient and advanced nanoparticle vaccines are of tremendous applicability in prevention of infectious diseases of fish. In this study, dihydrolipoamide dehydrogenase (DLDH) antigens of Vibrio alginolyticus were loaded into mesoporous silica nanoparticles (MSN) to compose the vaccine delivery system. Hydroxypropyl methylcellulose phthalate (HP55) was coated to provide protection of immunogen. The morphology, loading capacity, acid-base triggered release were characterized and the toxicity of nanoparticle vaccine was determined in vitro. Further, the vaccine immune effects were evaluated in large yellow croaker via oral administration. In vitro studies confirmed that the antigen could be stable in enzymes-rich artificial gastric fluid and released under artificial intestinal fluid environment. In vitro cytotoxicity assessment demonstrated the vaccines within 120 μg/ml have good biocompatibility for large yellow croaker kidney cells. Our data confirmed that the nanoparticle vaccine in vivo could elicit innate and adaptive immune response, and provide good protection against Vibrio alginolyticus challenge. The MSN delivery system prepared may be a potential candidate carrier for fish vaccine via oral administration feeding. Further, we provide theoretical basis for developing convenient, high-performance, and cost-efficient vaccine against infectious diseases in aquaculture.
研究领域:
水产养殖
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纳米技术
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免疫学
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兽医学
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DOI
PubMed
高影响因子
Catalysis Science & Technology
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2022
·Vol. 12
·期 14
·4486-4497
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IF 6.177
Si Liu,Zhenfu Wang,Kun Chen,Linling Yu,Qinghong Shi,Xiaoyan Dong,Yan Sun
Chiral amines are valuable intermediates widely applied in the pharmaceutical industry. As an alternative to classical synthetic methods for the production of chiral amines, biocatalytic cascade synthesis for these molecules from their alcohol precursors has been developed. However, currently available enzyme cascade systems remain unstable and unsustainable in the practice of chiral amine synthesis. Herein, the catalytic cascade system of chimeric amine dehydrogenase (AmDH) and alcohol dehydrogenase (ADH) fused with silica binding peptide (SiBP) was site-specifically co-immobilized on silica nanoparticles (SNPs). SiBP enabled the fusion enzymes to firmly bind to SNPs, and both the single immobilized enzymes showed higher catalytic efficiencies (kcat/Km) than their free counterparts to different degrees. Using 10 mM (S)-2-hexanol as the substrate, the co-immobilized enzyme system (SiBP–ADH&SiBP–AmDH@SNPs) showed 90% (R)-2-aminohexane yield after 48 h reaction, which was 1.85-fold higher than the free enzyme system due to the enhanced catalytic efficiency of the immobilized enzymes and the possible proximity effect of the SiBP–ADH&SiBP–AmDH@SNPs. The catalyst productivity of the SiBP–ADH&SiBP–AmDH@SNPs was 11 to 34 times higher than literature data, demonstrating the high economic benefits and catalytic efficiency of this system in producing chiral amines. SiBP–ADH&SiBP–AmDH@SNPs retained 87% of its original activity after eight cycles of reuse. These results highlighted the potential of the co-immobilization system for the effective and sustainable synthesis of chiral amines in industrial practice.
研究领域:
生物催化
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酶工程
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药物化学
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纳米技术
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DOI
高影响因子
Green Synthesis and Catalysis
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2025
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IF 6.3
Mengqian Song,Yu Li,Jinhui Feng,Shuhong Mao,Peiyuan Yao,Qiaqing Wu,Dunming Zhu
Chiral β-amino alcohols represent a significant structural motif in many biologically active molecules. Developing an efficient biocatalytic method for synthesizing chiral β-amino alcohols with structural diversity is highly desirable. In this study, enzymatic hydroxymethylation of aryl-aliphatic aldehydes by benzaldehyde lyases (BALs) enabled the synthesis of α-hydroxymethyl ketones at high substrate loadings (200 mmol/L - 300 mmol/L). And the reductive amination of diverse α-hydroxymethyl ketones by amine dehydrogenases (AmDHs) was conducted for synthesizing chiral β-amino alcohols in high isolated yields (60 %-79 %). Furthermore, a one-pot, two-step enzymatic process involving BAL-catalyzed hydroxymethylation of aldehydes and subsequent AmDH-catalyzed reductive amination was developed, enabling the synthesis of aromatic, aliphatic and aryl-aliphatic ( S )-β-amino alcohols from corresponding aldehydes in good to excellent isolated yields (56 %-96 %) and excellent enantioselectivity (>99 % ee ). The practical utility of this methodology was further demonstrated through the synthesis of key intermediates for antiviral drug Telaprevir or ATP competitive ERK inhibitor BVD-523.
研究领域:
有机化学
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生物催化
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酶学
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药物化学
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合成生物学
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不对称合成
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DOI
高影响因子
危险品化学品经营许可证（带存储）