Biocatalysed concurrent production of enantioenriched compounds through parallel interconnected kinetic asymmetric transformations

Rioz‐Martínez, Ana; Bisogno, Fabricio R.; Rodrı́guez, Cristina; Gonzalo, Gonzalo de; Lavandera, Iván; Pazmiño, Daniel E. Torres; Fraaije, Marco W.; Gotor, Vicente

doi:10.1039/b925377g

Cited by 43 publications

(31 citation statements)

References 58 publications

(29 reference statements)

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“…The reaction mixtures were extracted with ethyl acetate and analyzed by GC using a HP-1 column to determine the progress in conversion. HPLC on a Hewlett-Packard 1100 LC liquid chromatograph equipped with a Chiralcel OD column was employed to determine the optical purity of the formed ( R )-methyl phenyl sulfoxide (Rioz-Martínez et al 2010). …”

Section: Methodsmentioning

confidence: 99%

Investigating the coenzyme specificity of phenylacetone monooxygenase from Thermobifida fusca

Dudek

Pazmiño

Rodrı́guez

et al. 2010

Appl Microbiol Biotechnol

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Type I Baeyer–Villiger monooxygenases (BVMOs) strongly prefer NADPH over NADH as an electron donor. In order to elucidate the molecular basis for this coenzyme specificity, we have performed a site-directed mutagenesis study on phenylacetone monooxygenase (PAMO) from Thermobifida fusca. Using sequence alignments of type I BVMOs and crystal structures of PAMO and cyclohexanone monooxygenase in complex with NADP+, we identified four residues that could interact with the 2′-phosphate moiety of NADPH in PAMO. The mutagenesis study revealed that the conserved R217 is essential for binding the adenine moiety of the nicotinamide coenzyme while it also contributes to the recognition of the 2′-phosphate moiety of NADPH. The substitution of T218 did not have a strong effect on the coenzyme specificity. The H220N and H220Q mutants exhibited a ~3-fold improvement in the catalytic efficiency with NADH while the catalytic efficiency with NADPH was hardly affected. Mutating K336 did not increase the activity of PAMO with NADH, but it had a significant and beneficial effect on the enantioselectivity of Baeyer–Villiger oxidations and sulfoxidations. In conclusion, our results indicate that the function of NADPH in catalysis cannot be easily replaced by NADH. This finding is in line with the complex catalytic mechanism and the vital role of the coenzyme in BVMOs.

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Section: Methodsmentioning

confidence: 99%

Investigating the coenzyme specificity of phenylacetone monooxygenase from Thermobifida fusca

Dudek

Pazmiño

Rodrı́guez

et al. 2010

Appl Microbiol Biotechnol

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“…Only a few cofactor turnovers could be reached at high NAD + concentration and 5 mM 1 a , which was attributed to non‐overlapping process windows of both enzymes (Table 1, entries 4–5). In this regard, the parallel interconnected dynamic asymmetric transformation (PIDAT)23 developed here is highly competitive among all known biocatalytic DKRs of 1 a , with lowest cofactor concentration needed, highest product concentration and highest TTN of the biocatalyst reached.…”

Section: Resultsmentioning

confidence: 98%

“…23 Maximal efficiency is in theory attained when racemization is the most rapid event [equation ( 2 )]. Increasing the enzyme concentration usually correlated with decreased stereoselectivity and it was speculated that the too slow racemization, combined with imperfect enzyme stereoselectivity, could not provide a steady pool of the faster reacting enantiomer (e. g. k rac < k R ox < k S ox ) 11,21…”

Section: Resultsmentioning

confidence: 99%

Biocatalytic Parallel Interconnected Dynamic Asymmetric Disproportionation of α‐Substituted Aldehydes: Atom‐Efficient Access to Enantiopure (S)‐Profens and Profenols

2018

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The biocatalytic asymmetric disproportionation of aldehydes catalyzed by horse liver alcohol dehydrogenase (HLADH) was assessed in detail on a series of racemic 2‐arylpropanals. Statistical optimization by means of design of experiments (DoE) allowed the identification of critical interdependencies between several reaction parameters and revealed a specific experimental window for reaching an ′optimal compromise′ in the reaction outcome. The biocatalytic system could be applied to a variety of 2‐arylpropanals and granted access in a redox‐neutral manner to enantioenriched (S)‐profens and profenols following a parallel interconnected dynamic asymmetric transformation (PIDAT). The reaction can be performed in aqueous buffer at ambient conditions, does not rely on a sacrificial co‐substrate, and requires only catalytic amounts of cofactor and a single enzyme. The high atom‐efficiency was exemplified by the conversion of 75 mM of rac‐2‐phenylpropanal with 0.03 mol% of HLADH in the presence of ∼0.013 eq. of oxidized nicotinamide adenine dinucleotide (NAD+), yielding 28.1 mM of (S)‐2‐phenylpropanol in 96% ee and 26.5 mM of (S)‐2‐phenylpropionic acid in 89% ee, in 73% overall conversion. Isolated yield of 62% was obtained on 100 mg‐scale, with intact enantiopurities.

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“…In this study we explored the potential of several amino polyphosphazenes to covalently attach phenylacetone monooxygenase (PAMO) from Thermobifida fusca [28] and G6PDH. PAMO is an attractive BVMO since it is a thermostable protein able to selectively oxidize a range of ketones [29][30][31][32][33] and sulfides [34][35][36][37]. We report for the first time the attachment of PAMO on several polyphosphazene…”

Section: Introductionmentioning

confidence: 99%

Immobilized redox enzymatic catalysts: Baeyer–Villiger monooxygenases supported on polyphosphazenes

Cuetos

Rioz‐Martínez

Valenzuela

et al. 2012

Journal of Molecular Catalysis B: Enzymatic

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Abstract.A novel method has been employed for the selective covalent co-immobilization of a BaeyerVilliger monooxygenase (phenylacetone monooxygenase from Thermobifida fusca) and a NADPH recycling enzyme (glucose-6-phosphate dehydrogenase) on the same polyphosphazene carrier for the first time starting from {NP[O 2 C 12 H 8-x (NH 2 ) x ]} n , (x ranging from 0.5 to 2) using glutaraldehyde as connector. In all cases the preparation was active and it was found that the optimum proportion of amino groups in the starting polyphosphazene was 0.5 per monomer. The immobilized biocatalysts showed similar selectivity when compared with the isolated monooxygenase, demonstrating the potential of this novel type of immobilizing material, although their recyclability must still be improved.2

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Biocatalysed concurrent production of enantioenriched compounds through parallel interconnected kinetic asymmetric transformations

Cited by 43 publications

References 58 publications

Investigating the coenzyme specificity of phenylacetone monooxygenase from Thermobifida fusca

Investigating the coenzyme specificity of phenylacetone monooxygenase from Thermobifida fusca

Biocatalytic Parallel Interconnected Dynamic Asymmetric Disproportionation of α‐Substituted Aldehydes: Atom‐Efficient Access to Enantiopure (S)‐Profens and Profenols

Immobilized redox enzymatic catalysts: Baeyer–Villiger monooxygenases supported on polyphosphazenes

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