Publicación Artículo científico (article).

Chemoenzymatic Production of Enantiocomplementary 2‐Substituted 3‐Hydroxycarboxylic Acids from l‐α‐Amino Acids

Digital.CSIC. Repositorio Institucional del CSIC
Digital.CSIC. Repositorio Institucional del CSIC
  • Pickl, Mathias
  • Marín-Valls, Roser
  • Joglar, Jesús
  • Bujons, Jordi
  • Clapés Saborit, Pere
A two‐enzyme cascade reaction plus in situ oxidative decarboxylation for the transformation of readily available canonical and non‐canonical l‐α‐amino acids into 2‐substituted 3‐hydroxycarboxylic acid derivatives is described. The biocatalytic cascade consisted of an oxidative deamination of l‐α‐amino acids by an l‐α‐amino acid deaminase from Cosenzaea myxofaciens, rendering 2‐oxoacid intermediates, with an ensuing aldol addition reaction to formaldehyde, catalyzed by metal‐dependent (R)‐ or (S)‐selective carboligases namely 2‐oxo‐3‐deoxy‐l‐rhamnonate aldolase (YfaU) and ketopantoate hydroxymethyltransferase (KPHMT), respectively, furnishing 3‐substituted 4‐hydroxy‐2‐oxoacids. The overall substrate conversion was optimized by balancing biocatalyst loading and amino acid and formaldehyde concentrations, yielding 36–98% aldol adduct formation and 91–98% ee for each enantiomer. Subsequent in situ follow‐up chemistry via hydrogen peroxide‐driven oxidative decarboxylation afforded the corresponding 2‐substituted 3‐hydroxycarboxylic acid derivatives., This project has received funding from Ministerio de Ciencia e Innovación, Agencia Estatal de Investigación, Fondo Europeo de Desarrollo Regional (FEDER) (grants RTI2018‐094637‐B‐I00) and Programación Conjunta Internacional PCI2018‐092937 under the ERACoBioTech (European Union's Horizon 2020 research and innovation programme under grant agreement No [722361]. This research was funded in part by the Austrian Science Fund (FWF) [J 4227‐B21]. M. P. acknowledges funding by the Austrian FWF through an Erwin Schrödinger fellowship.. The PmaLAAD expression plasmid was a generous gift from Prof. Wolfgang Kroutil (University of Graz)., Peer reviewed

Digital.CSIC. Repositorio Institucional del CSIC

Digital.CSIC. Repositorio Institucional del CSIC
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Digital.CSIC. Repositorio Institucional del CSIC