Glutamate as an Efficient Amine Donor for the Synthesis of Chiral β‐ and γ‐Amino Acids Using Transaminase

Kim, Geon‐Hee; Jeon, Hyeongtag; Khobragade, Taresh P.; Patil, Mahesh D.; Sung, Sihyong; Yoon, Sanghan; Won, Yumi; Sarak, Sharad; Yun, Hyungdon

doi:10.1002/cctc.201802048

Cited by 20 publications

(6 citation statements)

References 48 publications

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“…One of the well-known examples of medications with β-amino acids as essential ingredients is sitagliptin, an inhibitor of dipeptidyl peptidase 4 that is used as an oral diabetic medication ( Savile et al, 2010 ; Kim et al, 2019 ; Khobragade et al, 2021 ; Kaur and Jana, 2023 ). In our previous research, the sitagliptin intermediate was produced employing TA from Ilumatobacter coccineus (TAIC, TA 3 ) from the ethyl 3-oxo-4-(2,4,5-trifluorophenyl) butanoate as a substrate ( Khobragade et al, 2023 ).…”

Section: Resultsmentioning

confidence: 99%

Dual-function transaminases with hybrid nanoflower for the production of value-added chemicals from biobased levulinic acid

Khobragade,

Giri,

Pagar

et al. 2023

Front. Bioeng. Biotechnol.

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The U.S. Department of Energy has listed levulinic acid (LA) as one of the top 12 compounds derived from biomass. LA has gained much attention owing to its conversion into enantiopure 4-aminopentanoic acid through an amination reaction. Herein, we developed a coupled-enzyme recyclable cascade employing two transaminases (TAs) for the synthesis of (S)-4-aminopentanoic acid. TAs were first utilized to convert LA into (S)-4-aminopentanoic acid using (S)-α-Methylbenzylamine [(S)-α-MBA] as an amino donor. The deaminated (S)-α-MBA i.e., acetophenone was recycled back using a second TAs while using isopropyl amine (IPA) amino donor to generate easily removable acetone. Enzymatic reactions were carried out using different systems, with conversions ranging from 30% to 80%. Furthermore, the hybrid nanoflowers (HNF) of the fusion protein were constructed which afforded complete biocatalytic conversion of LA to the desired (S)-4-aminopentanoic acid. The created HNF demonstrated storage stability for over a month and can be reused for up to 7 sequential cycles. A preparative scale reaction (100 mL) achieved the complete conversion with an isolated yield of 62%. Furthermore, the applicability of this recycling system was tested with different β-keto ester substrates, wherein 18%–48% of corresponding β-amino acids were synthesized. Finally, this recycling system was applied for the biosynthesis of pharmaceutical important drug sitagliptin intermediate ((R)-3-amino-4-(2,4,5-triflurophenyl) butanoic acid) with an excellent conversion 82%.

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Section: Resultsmentioning

confidence: 99%

Dual-function transaminases with hybrid nanoflower for the production of value-added chemicals from biobased levulinic acid

Khobragade,

Giri,

Pagar

et al. 2023

Front. Bioeng. Biotechnol.

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“…369 In the presence of an (S)-transaminase from E. aerosaccus the b-oxoacid was subsequently converted to L-290 at the expense of 3-aminobutyric acid (240) as the amine donor (82% conversion to product, 499% ee). (S)-transaminases from Sphaerobacter thermophilus, 370,371 Polaromonas sp. 372 and a b-amino acid dehydrogenase from Candidatus cloacamonas acidaminovorans have also been proven capable of catalysing said transformation.…”

Section: Scheme 55 Chemoenzymatic Route Towards Oseltamivir As Develomentioning

confidence: 99%

Biocatalytic routes to anti-viral agents and their synthetic intermediates

Slagman

Fessner

2021

Chem. Soc. Rev.

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“…It has been reported that use of purified enzyme system for biocatalytic purposes costs approximately ten times more than that by whole-cell biotransformations [43,44]. Although the use of purified enzymes is limited for their application on large scales, another form of biocatalysts, i.e., cell-free extracts, is feasible if expression levels of the target protein are sufficient [45,46]. However, cell free extracts are unstable.…”

Section: Kinetic Resolution Of Racemic Amines Using E Coli Whole Celmentioning

confidence: 99%

Kinetic Resolution of Racemic Amines to Enantiopure (S)-amines by a Biocatalytic Cascade Employing Amine Dehydrogenase and Alanine Dehydrogenase

et al. 2019

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Amine dehydrogenases (AmDHs) efficiently catalyze the NAD(P)H-dependent asymmetric reductive amination of prochiral carbonyl substrates with high enantioselectivity. AmDH-catalyzed oxidative deamination can also be used for the kinetic resolution of racemic amines to obtain enantiopure amines. In the present study, kinetic resolution was carried out using a coupled-enzyme cascade consisting of AmDH and alanine dehydrogenase (AlaDH). AlaDH efficiently catalyzed the conversion of pyruvate to alanine, thus recycling the nicotinamide cofactors and driving the reaction forward. The ee values obtained for the kinetic resolution of 25 and 50 mM rac-α-methylbenzylamine using the purified enzymatic systems were only 54 and 43%, respectively. The use of whole-cells apparently reduced the substrate/product inhibition, and the use of only 30 and 40 mgDCW/mL of whole-cells co-expressing AmDH and AlaDH efficiently resolved 100 mM of rac-2-aminoheptane and rac-α-methylbenzylamine into the corresponding enantiopure (S)-amines. Furthermore, the applicability of the reaction protocol demonstrated herein was also successfully tested for the efficient kinetic resolution of wide range of racemic amines.

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Glutamate as an Efficient Amine Donor for the Synthesis of Chiral β‐ and γ‐Amino Acids Using Transaminase

Cited by 20 publications

References 48 publications

Dual-function transaminases with hybrid nanoflower for the production of value-added chemicals from biobased levulinic acid

Dual-function transaminases with hybrid nanoflower for the production of value-added chemicals from biobased levulinic acid

Biocatalytic routes to anti-viral agents and their synthetic intermediates

Kinetic Resolution of Racemic Amines to Enantiopure (S)-amines by a Biocatalytic Cascade Employing Amine Dehydrogenase and Alanine Dehydrogenase

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