Opposite Enantioselectivity in the Bioreduction of (Z)‐β‐Aryl‐β‐cyanoacrylates Mediated by the Tryptophan 116 Mutants of Old Yellow Enzyme 1: Synthetic Approach to (R)‐ and (S)‐β‐Aryl‐γ‐lactams

Abstract

TheT rp 116 mutantso fO ld Yellow Enzyme 1t hat catalyse the reductiono f( Z )-b-arylb-cyanoacrylates give the opposite enantioselectivity according to the nature of the amino acid in position 116. Small amino acids (e.g.,a lanine)m aket he substrate bind to the enzyme'sa ctive site in a" classical" orientation, affording the (S)-enantiomer of the reduced product.W hen the size of the amino acid increases( e.g.,l eucine), a" flipped" binding mode is adopted by the substrate,w hich is converted into the corresponding (R)-derivative.W ith bulky amino acids (e.g.,t ryptophan in the wild-type) the reduction does not occur. Thee nantiomerically enriched cyanopropanoates thus prepared can be converted into the corresponding (S)-and (R)-b-aryl-g-lactams, precursors of inhibitory neurotransmitters belonging to the class of g-aminobutyrica cids,b yasimple functional group interconversion in as equential onepot procedure.

Revealing Additional Stereocomplementary Pairs of Old Yellow Enzymes by Rational Transfer of Engineered Residues

“…No activity towards 1 was observed with PETNR W102I, but other variants at this hotspot position and other substrates showed increased conversion . Incorporation of W116I into circular permutated OYE1 variants lowered conversion of 3 , a saturation mutagenesis library at W116 showed no hits for 1 , and biocatalytic characterisation of all 20 variants showed that W116I is not the best engineered residue for this position . Nevertheless, our NCR data support the importance of hotspot position III itself.…”

“…Nevertheless, our NCR data support the importance of hotspot position III itself. Taking all evidence together, it appears that residues at hotspot position III are fine‐tuning reactivity, either alone or together with other hotspot positions …”

Old Yellow Enzyme-Catalysed Asymmetric Hydrogenation: Linking Family Roots with Improved Catalysis

“…Substitution against more bulky residues resulted in a switch of stereoselectivity affording the (R)-enantiomer. This tryptophan is conserved for classes I and II enzymes and might be a major residue for changing enantioselectivity of different prochiral substrates [25]. Class III enzymes possess a conserved alanine at this position.…”

“…Catalysts 2017, 7, 130 2 of 24 activated alkenes with an electron withdrawing group (EWG) such as aldehyde, ketone, anhydride [8,10,11], nitro [9,12,13], (di)ester [8,[14][15][16][17], (di)carboxylic acid [18][19][20], cyclic imide [21][22][23], nitrile [24], β-cyanoacrylate [25], β-nitroacrylate [26], and several other functional groups [27]. There are many examples of the high industrial potential of OYEs for the synthesis of valuable target products [28][29][30][31].…”

Biocatalytic Approach to Chiral β-Nitroalcohols by Enantioselective Alcohol Dehydrogenase-Mediated Reduction of α-Nitroketones

“…The scarcity of experimental data on the bioreduction of -nitroketones, especially for aromatic derivatives, and the current need for biocatalysed synthesis of chiral building blocks for pharmaceutical applications [27][28][29][30][31] led us to investigate the use of commercial alcohol dehydrogenases for the enantioselective reduction of aryl and alkyl α-nitroketones 3 in controlled reaction conditions. We also studied the further manipulation of specific nitroalcohols 1 to prepare aminoalcohols 2, which have been already employed as key intermediates for the synthesis of active pharmaceutical ingredients, such as levamisole and (R)-tembamide.…”