Simultaneous enzymatic synthesis of ( S )-3-fluoroalanine and ( R )-3-fluorolactic acid

Gonçalves, Luciana P.B.; Antunes, Octávio Augusto Ceva; Pinto, Gerson F.; Oestreicher, Enrique G.

doi:10.1016/s0957-4166(00)00096-3

Cited by 40 publications

(26 citation statements)

References 7 publications

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“…3-Fluoro-D-alanine or (S)-3-fluoroalanine is recognized as a wide spectrum of antibiotic that can irreversibly inactivate bacterial alanine racemase which is an enzyme involved in the biosynthesis of cell wall [3,5]. This compound also acts as an inhibitor of serine palmitosyl transferase and in addition, it is a potential precursor of fluoroamine compounds [3,5].…”

Section: Introductionmentioning

confidence: 98%

“…In addition, the enzymatic synthesis of amino acids has been examined in both academic and industrial research for over a century [2]. Fluorinated α-amino acids are considered to be highly versatile chiral building blocks for the asymmetric synthesis of several compounds of pharmacological interest [3]. Amino acids and large molecules containing fluorine have been used for medical applications such as control of blood pressure, allergies, and tumor growth.…”

Section: Introductionmentioning

confidence: 99%

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Asymmetric synthesis of (R)-3-fluoroalanine from 3-fluoropyruvate using omega-transaminase

Bea

Lee

Yun

2011

Biotechnol Bioproc E

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In this study, (R)-3-fluoroalanine was asymmetrically synthesized from 3-fluoropyruvate (F-pyruvate) and (S)-α-methylbenzylamine (MBA) using recombinant ω-transaminase (TA) from Vibrio fluvialis JS17. The reaction was severely inhibited by acetophenone (deaminated product of α-MBA). In the presence of 5 mM acetophenone, the reactivity of the enzyme towards F-pyruvate decreased by 78%. To overcome the product inhibition by acetophenone, a biphasic reaction was successfully used. The conversion of F-pyruvate into (R)-3-fluoroalanine (enatiomeric exess (e.e.) > 99%) was about 95% in the biphasic system (75 mM F-pyruvate, 100 mM (S)-α-MBA, and 3.0 U/mL), whereas 31% was obtained without product extraction. The use of racemic α-MBA as an amino donor instead of (S)-α-MBA can reduce the reaction cost and also produce chiral amines through kinetic resolution. When the kinetic resolution of racemic α-MBA (40 mM) was carried out with F-pyruvate (30 mM) and ω-TA (3.0 U/mL) in 100 mM phosphate buffer (pH 7.0), the e.e. of (R)-α-MBA reached 98.4% with 52.2% conversion for 10 h and 21 mM (R)-3-fluoroalanine was produced with 70% conversion and an e.e. > 99%.

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Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Asymmetric synthesis of (R)-3-fluoroalanine from 3-fluoropyruvate using omega-transaminase

Bea

Lee

Yun

2011

Biotechnol Bioproc E

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“…An early example is the transformation of racemic lactate into l-alanine via the intermediate pyruvate, employing a combination of dand l-lactate DHs with l-AlaDH as biocatalysts [17]. Another reaction cascade involving BasAlaDH was reported for the production of (S)-3-fluoroalanine, a potent antibiotic agent [18], via kinetic resolution of racemic 3-fluoroalanine by stereospecific oxidative deamination [19].…”

Section: Introductionmentioning

confidence: 98%

Engineering of alanine dehydrogenase from Bacillus subtilis for novel cofactor specificity

Lerchner

Jarasch

Skerra

2015

Biotech and App Biochem

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The l-alanine dehydrogenase of Bacillus subtilis (BasAlaDH), which is strictly dependent on NADH as redox cofactor, efficiently catalyzes the reductive amination of pyruvate to l-alanine using ammonia as amino group donor. To enable application of BasAlaDH as regenerating enzyme in coupled reactions with NADPH-dependent alcohol dehydrogenases, we alterated its cofactor specificity from NADH to NADPH via protein engineering. By introducing two amino acid exchanges, D196A and L197R, high catalytic efficiency for NADPH was achieved, with k /K = 54.1 µM Min (K = 32 ± 3 µM; k = 1,730 ± 39 Min ), almost the same as the wild-type enzyme for NADH (k /K = 59.9 µM Min ; K = 14 ± 2 µM; k = 838 ± 21 Min ). Conversely, recognition of NADH was much diminished in the mutated enzyme (k /K = 3 µM Min ). BasAlaDH(D196A/L197R) was applied in a coupled oxidation/transamination reaction of the chiral dicyclic dialcohol isosorbide to its diamines, catalyzed by Ralstonia sp. alcohol dehydrogenase and Paracoccus denitrificans ω-aminotransferase, thus allowing recycling of the two cosubstrates NADP and l-Ala. An excellent cofactor regeneration with recycling factors of 33 for NADP and 13 for l-Ala was observed with the engineered BasAlaDH in a small-scale biocatalysis experiment. This opens a biocatalytic route to novel building blocks for industrial high-performance polymers.

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“…Therefore, enzymatic production strategies have been extensively studied for this end and some of them have been successfully commercialized (Rouhi 2004;Schmid et al 2001;Schoemaker et al 2003). For example, commercial-scale production processes have been developed via kinetic resolution using amidase, hydantoinase, nitrilase, and acylase (Schmid et al 2001), and asymmetric synthesis using transaminase and dehydrogenase (Gonalves et al 2000;Hanzawa et al 2001;Li et al 2002;Stewart 2001). Asymmetric synthesis is usually preferred over kinetic resolution because theoretically attainable yield becomes doubled, given that cheap substrates are available.…”

Section: Introductionmentioning

confidence: 99%

Transaminase-catalyzed asymmetric synthesis of l-2-aminobutyric acid from achiral reactants

Shin

Kim

2009

Biotechnol Lett

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Asymmetric synthesis of an unnatural amino acid was demonstrated by omega-transaminase from Vibrio fluvialis JS17. L-2-Aminobutyric acid was synthesized from 2-oxobutyric acid and benzylamine with an enantiomeric excess higher than 99%. The reaction showed severe product inhibition by benzaldehyde, which was overcome by employing a biphasic reaction system to remove the inhibitory product from the aqueous phase. In a typical biphasic reaction (50 mM 2-oxobutyric acid, 70 mM benzylamine and 2.64 U/ml purified enzyme) using hexane as an extractant, conversion of 2-oxobutyric acid reached 96% in 5 h whereas only 39% conversion was obtained without the product extraction.

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Simultaneous enzymatic synthesis of ( S )-3-fluoroalanine and ( R )-3-fluorolactic acid

Cited by 40 publications

References 7 publications

Asymmetric synthesis of (R)-3-fluoroalanine from 3-fluoropyruvate using omega-transaminase

Asymmetric synthesis of (R)-3-fluoroalanine from 3-fluoropyruvate using omega-transaminase

Engineering of alanine dehydrogenase from Bacillus subtilis for novel cofactor specificity

Transaminase-catalyzed asymmetric synthesis of l-2-aminobutyric acid from achiral reactants

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