Asymmetric Reductive Amination of Structurally Diverse Ketones with Ammonia Using a Spectrum-Extended Amine Dehydrogenase

ACS Catalysis ◽  
2021 ◽  
pp. 14274-14283
Author(s):  
Dong-Hao Wang ◽  
Qi Chen ◽  
Sai-Nan Yin ◽  
Xu-Wei Ding ◽  
Yu-Cong Zheng ◽  
...  
Keyword(s):  
Reductive Amination ◽  
Amine Dehydrogenase

scholarly journals Economy Assessment for the Chiral Amine Production with Comparison of Reductive Amination and Transamination Routes by Multi-Enzyme System

Catalysts ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1451
Author(s):  
Heyu Huo ◽  
Guangxiao Yao ◽  
Shizhen Wang
Keyword(s):  
Reductive Amination ◽  
Nadh Oxidase ◽  
Glucose Dehydrogenase ◽  
Economic Assessment ◽  
Building Blocks ◽  
Unit Price ◽  
Chiral Amine ◽  
Process Comparison ◽  
Amine Dehydrogenase

Chiral amines are key building blocks for pharmaceuticals. Economic assessment of commercial potential of bioprocesses is needed for guiding research. Biosynthesis of (S)-α-methylbenzylamine (MBA) was selected as case study. For transamination route, transaminase coupled with glucose dehydrogenase and lactate dehydrogenase catalyzed the reaction with NADH (Nicotinamide adenine dinucleotide) regeneration. Amine dehydrogenase coupled with NADH oxidase, which catalyzed the reductive amination process. Comparison of biosynthesis cost by reductive amination and transamination routes was carried out. Economic assessment based on the framework of cost analysis and preliminary process information revealed that cost is greatly dependent on enzyme price. The results indicated that enhancing the activity of amine dehydrogenase by 4–5 folds can drop the unit price of reductive amination to $0.5–0.6/g, which make it competitive with transamination route.

Reductive Amination of Biobased Levulinic Acid to Unnatural Chiral γ-Amino Acid Using an Engineered Amine Dehydrogenase

2020 ◽  
Vol 8 (46) ◽  
pp. 17054-17061
Author(s):  
Rui-Feng Cai ◽  
Lei Liu ◽  
Fei-Fei Chen ◽  
Aitao Li ◽  
Jian-He Xu ◽  
...  
Keyword(s):  
Amino Acid ◽  
Levulinic Acid ◽  
Reductive Amination ◽  
Amine Dehydrogenase

scholarly journals Biosynthesis of Chiral Amino Alcohols via an Engineered Amine Dehydrogenase in E. coli

2022 ◽  
Vol 9 ◽  
Author(s):  
Feifei Tong ◽  
Zongmin Qin ◽  
Hongyue Wang ◽  
Yingying Jiang ◽  
Junkuan Li ◽  
...  
Keyword(s):  
Reductive Amination ◽  
Asymmetric Reduction ◽  
Amino Alcohols ◽  
Saturation Mutagenesis ◽  
Preparative Scale ◽  
One Step ◽  
Amine Dehydrogenase ◽  
The One ◽  
Total Turnover ◽  
Chiral Amino Alcohols

Chiral amino alcohols are prevalent synthons in pharmaceuticals and synthetic bioactive compounds. The efficient synthesis of chiral amino alcohols using ammonia as the sole amino donor under mild conditions is highly desired and challenging in organic chemistry and biotechnology. Our previous work explored a panel of engineered amine dehydrogenases (AmDHs) derived from amino acid dehydrogenase (AADH), enabling the one-step synthesis of chiral amino alcohols via the asymmetric reductive amination of α-hydroxy ketones. Although the AmDH-directed asymmetric reduction is in a high stereoselective manner, the activity is yet fully excavated. Herein, an engineered AmDH derived from a leucine dehydrogenase from Sporosarcina psychrophila (SpAmDH) was recruited as the starting enzyme, and the combinatorial active-site saturation test/iterative saturation mutagenesis (CAST/ISM) strategy was applied to improve the activity. After three rounds of mutagenesis in an iterative fashion, the best variant wh84 was obtained and proved to be effective in the asymmetric reductive amination of 1-hydroxy-2-butanone with 4-fold improvements in kcat/Km and total turnover number (TTN) values compared to those of the starting enzyme, while maintaining high enantioselectivity (ee >99%) and thermostability (T5015 >53°C). In preparative-scale reaction, the conversion of 100 and 200 mM 1-hydroxy-2-butanone catalyzed by wh84 was up to 91–99%. Insights into the source of an enhanced activity were gained by the computational analysis. Our work expands the catalytic repertoire and toolbox of AmDHs.

Asymmetric reductive amination by a wild-type amine dehydrogenase from the thermophilic bacteria Petrotoga mobilis

2016 ◽  
Vol 6 (20) ◽  
pp. 7421-7428 ◽  
Author(s):  
Ombeline Mayol ◽  
Sylvain David ◽  
Ekaterina Darii ◽  
Adrien Debard ◽  
Aline Mariage ◽  
...  
Keyword(s):  
Primary Amine ◽  
Reductive Amination ◽  
Thermophilic Bacteria ◽  
Wild Type ◽  
Enantiomerically Pure ◽  
Amine Dehydrogenase

Biocatalytic potential of a new wild-type amine dehydrogenase used in an enzyme-catalyzed synthesis of an enantiomerically pure primary amine.

Engineering of Amine Dehydrogenase for Asymmetric Reductive Amination of Ketone by Evolving Rhodococcus Phenylalanine Dehydrogenase

ACS Catalysis ◽  
2015 ◽  
Vol 5 (2) ◽  
pp. 1119-1122 ◽  
Author(s):  
Li Juan Ye ◽  
Hui Hung Toh ◽  
Yi Yang ◽  
Joseph P. Adams ◽  
Radka Snajdrova ◽  
...  
Keyword(s):  
Reductive Amination ◽  
Phenylalanine Dehydrogenase ◽  
Amine Dehydrogenase

The Reductive Amination of Carbonyl Compounds Using Native Amine Dehydrogenase from Laribacter hongkongensis

2021 ◽  
Vol 26 (3) ◽  
pp. 384-391
Author(s):  
Somin Lee ◽  
Hyunwoo Jeon ◽  
Pritam Giri ◽  
Uk-Jae Lee ◽  
Hyunsang Jung ◽  
...  
Keyword(s):  
Carbonyl Compounds ◽  
Reductive Amination ◽  
Laribacter Hongkongensis ◽  
Amine Dehydrogenase

Selective Functionalization at N2-Position of Guanine in Oligonucleotides via Reductive Amination

2020 ◽  
Author(s):  
Bapurao Bhoge ◽  
Ishu Saraogi
Keyword(s):  
Organic Chemistry ◽  
Chemical Biology ◽  
Reductive Amination ◽  
The Other ◽  
Dna Oligomers ◽  
Site Specific ◽  
Wide Applicability ◽  
Dna Oligonucleotides ◽  
Selective Functionalization

Chemo- and site-specific modifications in oligonucleotides have wide applicability as mechanistic probes in chemical biology. Here we have employed a classical reaction in organic chemistry, reductive amination, to selectively functionalize the N<sup>2</sup>-amine of guanine/2’-deoxyguanine monophosphate. This method specifically modifies guanine in several tested DNA oligonucleotides, while leaving the other bases unaffected. Using this approach, we have successfully incorporated desired handles chemoselectively into DNA oligomers.

Bringing Biocatalysis into the Deuteration Toolbox

2019 ◽  
Author(s):  
Jack Rowbotham ◽  
Oliver Lenz ◽  
Holly Reeve ◽  
Kylie Vincent
Keyword(s):  
Late Stage ◽  
Hydrogen Isotope ◽  
Reductive Amination ◽  
Mechanistic Studies ◽  
Ambient Conditions ◽  
Synthetic Pathway ◽  
Drug Candidates ◽  
Isotopic Selectivity ◽  
Reducing Equivalents

<p></p><p>Chemicals labelled with the heavy hydrogen isotope deuterium (<sup>2</sup>H) have long been used in chemical and biochemical mechanistic studies, spectroscopy, and as analytical tracers. More recently, demonstration of selectively deuterated drug candidates that exhibit advantageous pharmacological traits has spurred innovations in metal-catalysed <sup>2</sup>H insertion at targeted sites, but asymmetric deuteration remains a key challenge. Here we demonstrate an easy-to-implement biocatalytic deuteration strategy, achieving high chemo-, enantio- and isotopic selectivity, requiring only <sup>2</sup>H<sub>2</sub>O (D<sub>2</sub>O) and unlabelled dihydrogen under ambient conditions. The vast library of enzymes established for NADH-dependent C=O, C=C, and C=N bond reductions have yet to appear in the toolbox of commonly employed <sup>2</sup>H-labelling techniques due to requirements for suitable deuterated reducing equivalents. By facilitating transfer of deuterium atoms from <sup>2</sup>H<sub>2</sub>O solvent to NAD<sup>+</sup>, with H<sub>2</sub> gas as a clean reductant, we open up biocatalysis for asymmetric reductive deuteration as part of a synthetic pathway or in late stage functionalisation. We demonstrate enantioselective deuteration via ketone and alkene reductions and reductive amination, as well as exquisite chemo-control for deuteration of compounds with multiple unsaturated sites.</p><p></p>

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