Enzymatic synthesis of chiral γ-amino acids using ω-transaminase

Shon, Minsu; Shanmugavel, R.; Shin, Giyoung; Mathew, Sam; Lee, Sang‐Hyeup; Yun, Hyungdon

doi:10.1039/c3cc44864a

Cited by 22 publications

(17 citation statements)

References 37 publications

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“…The reaction in which ( S )‐α‐MBA was used gave 9.5 mM of ( R )‐3a with a high optical purity ( ee > 99%), whereas the other amino donors gave less than 0.9 mM of ( R )‐3a. Previously, while synthesizing γ‐amino acids via asymmetric synthesis using ω‐TAPo, ( S )‐α‐MBA was screened as the best amino donor . Consequently, ( S )‐α‐MBA was selected as the amino donor for the asymmetric synthesis.…”

Section: Resultsmentioning

confidence: 99%

Asymmetric synthesis of aromatic β‐amino acids using ω‐transaminase: Optimizing the lipase concentration to obtain thermodynamically unstable β‐keto acids

Mathew

Jeong

Chung

et al. 2015

Biotechnology Journal

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Synthesized aromatic β-amino acids have recently attracted considerable attention for their application as precursors in many pharmacologically relevant compounds. Previous studies on asymmetric synthesis of aromatic β-amino acids using ω-transaminases could not be done efficiently due to the instability of β-keto acids. In this study, a strategy to circumvent the instability problem of β-keto acids was utilized to generate β-amino acids efficiently via asymmetric synthesis. In this work, thermodynamically stable β-ketoesters were initially converted to β-keto acids using lipase, and the β-keto acids were subsequently aminated using ω-transaminase. By optimizing the lipase concentration, we successfully overcame the instability problem of β-keto acids and enhanced the production of β-amino acids. This strategy can be used as a general approach to efficiently generate β-amino acids from β-ketoesters.

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Section: Resultsmentioning

confidence: 99%

Asymmetric synthesis of aromatic β‐amino acids using ω‐transaminase: Optimizing the lipase concentration to obtain thermodynamically unstable β‐keto acids

Mathew

Jeong

Chung

et al. 2015

Biotechnology Journal

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“…Enantiopure amines, β‐and γ‐amino acids serve as building blocks for many industrially important pharmaceuticals, agricultural and fine chemicals. TAs have increasingly been used in the synthesis of these chiral building blocks . TA‐mediated reductive amination of prochiral ketones to their corresponding amines, often suffers from inhibition of the enzyme by co‐product, and unfavorable thermodynamic equilibrium ,.…”

Section: Methodsmentioning

confidence: 99%

“…Based on their enantioselectivity, TAs generally are classified into ( S )‐ and ( R )‐selective enzymes . However, there is a subgroup of ( S )‐TAs, which exhibits activity not only toward amines but also toward β and γ‐amino acids ,. Due to the importance of β and γ‐amino acids,, their synthesis has been studied by employing TAs belonging to this subgroup ,.…”

Section: Methodsmentioning

confidence: 99%

“…However, the screening and designing of efficient amine donors for the synthesis of γ‐ and β‐amino acids are relatively less studied compared with that for chiral amines. Currently, ( S )‐α‐methylbenzylamine (( S )‐α‐MBA) is the most frequently used amine donor to produce β‐ and γ‐amino acids ,,. However, ( S )‐α‐MBA is relatively expensive, and the use of ( S )‐α‐MBA causes severe product inhibition of the enzyme by acetophenone ,.…”

Section: Methodsmentioning

confidence: 99%

“…Currently, ( S )‐α‐methylbenzylamine (( S )‐α‐MBA) is the most frequently used amine donor to produce β‐ and γ‐amino acids ,,. However, ( S )‐α‐MBA is relatively expensive, and the use of ( S )‐α‐MBA causes severe product inhibition of the enzyme by acetophenone ,. Furthermore, reaction engineering strategies, such as biphasic reaction system, are often needed to circumvent the product inhibition .…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2019

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A recyclable glutamate amine donor system employing transaminase (TA), glutamate dehydrogenase (GluDH) and mutant formate dehydrogenase (FDHm) was developed, wherein amine donor Glu was regenerated using GluDH and thereby circumvented the inhibition of TA by α‐ketoglutarate. Various enantiopure β‐, γ‐amino acids, and amines were successfully synthesized with high conversions and excellent enantiomeric excess using this system.

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Asymmetric Biocatalytic Synthesis of Fluorinated Pyridines through Transesterification or Transamination: Computational Insights into the Reactivity of Transaminases

et al. 2017

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Abstract. The synthesis of a family of pyridines bearing a fluorinated substituent on the aromatic ring has been carried out through two independent and highly stereoselective chemoenzymatic strategies. Short chemical synthetic routes toward fluorinated racemic amines and prochiral ketones have been developed, which served as substrates to explore the suitability of lipases and transaminases in asymmetric biotransformations. The lipase-catalyzed kinetic resolution via acylation of racemic amines proceeded smoothly giving conversions close to 50% and excellent enantioselectivities. Alternatively, the biotransamination of the corresponding prochiral ketones was investigated giving access to both optically pure amine enantiomers using transaminases with complementary selectivity. High to quantitative conversion values were achieved, which allowed the isolation of the amines in moderate to high yields (40-88%). A deeper understanding of the latter process was enabled by performing theoretical calculations on thermodynamic and mechanistic aspects. Calculations showed that the biotransamination reactions are highly favoured by the presence of fluorine atoms and the pyridine ring.

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Enzymatic synthesis of chiral γ-amino acids using ω-transaminase

Cited by 22 publications

References 37 publications

Asymmetric synthesis of aromatic β‐amino acids using ω‐transaminase: Optimizing the lipase concentration to obtain thermodynamically unstable β‐keto acids

Asymmetric synthesis of aromatic β‐amino acids using ω‐transaminase: Optimizing the lipase concentration to obtain thermodynamically unstable β‐keto acids

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

Asymmetric Biocatalytic Synthesis of Fluorinated Pyridines through Transesterification or Transamination: Computational Insights into the Reactivity of Transaminases

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