Alcaligenes faecalis penicillin G acylase-catalyzed enantioselective acylation of dl-phenylalanine and derivatives in aqueous medium

Gong, Xiangyu; Su, Erzheng; Wang, Pixiang; Wei, Dongzhi

doi:10.1016/j.tetlet.2011.08.056

Cited by 20 publications

(2 citation statements)

References 24 publications

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“…Using the optimal reaction conditions set-up by analytical scale biotransformations, the preparative scale biotransformation provided similarly high conversion and ee values, affording the corresponding d - and l - amino acids in good conversions, isolated yields and optical purities (Table 4). The efficiency of ammonia eliminations, in terms of yields and enantiomeric excess values, are comparable with the kinetic resolutions performed with purified/commercial enzymes, such as the penicillin G acylase mediated enantioselective acylation for d - p -methylphenylalanine d - 1c 44 , or the l -AAO/catalase catalyzed kinetic resolution process yielding d - m -(trifluoromethyl)phenylalanine d - 1k 45 , a key chiral intermediate for ( R )-PFI-2 33 . Definitely, in terms of conversions the kinetic resolution-type ammonia elimination of rac - 1c is surpassed by the asymmetric synthetic routes, such as the reductive amination of the corresponding keto-acid catalyzed by DAADH ( d -amino acid dehydrogenase) 46 , necessitating co-factor (NADPH) regeneration system or the l -amino acid deaminase and engineered aminotransferase coupled cascade, that uses l - or racemic amino acid 1c as starting material 47 .…”

Section: Resultsmentioning

confidence: 74%

The production of l- and d-phenylalanines using engineered phenylalanine ammonia lyases from Petroselinum crispum

Tork

Nagy

Cserepes

et al. 2019

Sci Rep

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The biocatalytic synthesis of l- and d-phenylalanine analogues of high synthetic value have been developed using as biocatalysts mutant variants of phenylalanine ammonia lyase from Petroselinum crispum (PcPAL), specifically tailored towards mono-substituted phenylalanine and cinnamic acid substrates. The catalytic performance of the engineered PcPAL variants was optimized within the ammonia elimination and ammonia addition reactions, focusing on the effect of substrate concentration, biocatalyst:substrate ratio, reaction buffer and reaction time, on the conversion and enantiomeric excess values. The optimal conditions provided an efficient preparative scale biocatalytic procedure of valuable phenylalanines, such as (S)-m-methoxyphenylalanine (Y = 40%, ee > 99%), (S)-p-bromophenylalanine (Y = 82%, ee > 99%), (S)-m-(trifluoromethyl)phenylalanine (Y = 26%, ee > 99%), (R)-p-methylphenylalanine, (Y = 49%, ee = 95%) and (R)-m-(trifluoromethyl)phenylalanine (Y = 34%, ee = 93%).

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Section: Resultsmentioning

confidence: 74%

The production of l- and d-phenylalanines using engineered phenylalanine ammonia lyases from Petroselinum crispum

Tork

Nagy

Cserepes

et al. 2019

Sci Rep

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“…29 Exploiting the substrate promiscuity, this enzyme class has also been utilized in the synthesis of dipeptides 30,31 and the kinetic resolution of amines. 32,33 For example, immobilized PGA was utilized for the resolution of the β-aminoester 11 using 7 as an acyl donor, resulting in an enantiopure precursor for the platelet aggregation inhibitor xemilofiban (S)-11 on a 70 L scale (Scheme 3C). 34 Recently, PGA has been utilized by researchers at Merck for larger biomolecules.…”

Section: Penicillin G Acylasesmentioning

confidence: 99%

Biocatalytic amide bond formation

2023

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Current state and perspectives of penicillin G acylase-based biocatalyses

Marešová

Plačková

Grulich

et al. 2014

Appl Microbiol Biotechnol

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In the course of more than 60-year history, penicillin G acylase (PGA) gained a unique position among enzymes used by pharmaceutical industry for production of β-lactam antibiotics. Kinetically controlled enzymatic syntheses of cephalosporins of novel generations in which PGA catalyzes coupling of activated acyl donor with nucleophile belong among the latest large-scale applications. Contrary to rather specific roles of other enzymes involved in β-lactam biocatalyses, the PGA seems to have the greatest potential. On the laboratory scale, other applications with industrial potential were described, e.g., directed evolution of the enzyme to meet specific demands of industrial processes or its modification into the enzyme catalyzing reactions with novel substrates. The fact that β-lactams represent the most important group of antibiotics comprising 65 % of the world antibiotic market explains such a tremendous and continuous interest in this enzyme. Indeed, the annual consumption of PGA has recently been estimated to range from 10 to 30 million tons. The application potential of the enzyme goes beyond the β-lactam biocatalysis due to its enantioselectivity and promiscuity: the PGA can be used for the production of achiral and chiral compounds convenient for the preparation of synthons and active pharmaceutical ingrediences, respectively. These biocatalyses, however, still wait for large-scale application.

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Alcaligenes faecalis penicillin G acylase-catalyzed enantioselective acylation of dl-phenylalanine and derivatives in aqueous medium

Cited by 20 publications

References 24 publications

The production of l- and d-phenylalanines using engineered phenylalanine ammonia lyases from Petroselinum crispum

The production of l- and d-phenylalanines using engineered phenylalanine ammonia lyases from Petroselinum crispum

Biocatalytic amide bond formation

Current state and perspectives of penicillin G acylase-based biocatalyses

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