Phenylalanine Ammonia-Lyase-Catalyzed Deamination of an Acyclic Amino Acid: Enzyme Mechanistic Studies Aided by a Novel Microreactor Filled with Magnetic Nanoparticles

Chembiochem : a European Journal of Chemical Biology
Diána WeiserL Poppe

Abstract

Phenylalanine ammonia-lyase (PAL), found in many organisms, catalyzes the deamination of l-phenylalanine (Phe) to (E)-cinnamate by the aid of its MIO prosthetic group. By using PAL immobilized on magnetic nanoparticles and fixed in a microfluidic reactor with an in-line UV detector, we demonstrated that PAL can catalyze ammonia elimination from the acyclic propargylglycine (PG) to yield (E)-pent-2-ene-4-ynoate. This highlights new opportunities to extend MIO enzymes towards acyclic substrates. As PG is acyclic, its deamination cannot involve a Friedel-Crafts-type attack at an aromatic ring. The reversibility of the PAL reaction, demonstrated by the ammonia addition to (E)-pent-2-ene-4-ynoate yielding enantiopure l-PG, contradicts the proposed highly exothermic single-step mechanism. Computations with the QM/MM models of the N-MIO intermediates from L-PG and L-Phe in PAL show similar arrangements within the active site, thus supporting a mechanism via the N-MIO intermediate.

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Citations

Apr 14, 2017·Organic & Biomolecular Chemistry·László Csaba BenczeCsaba Paizs
May 13, 2017·Chemical Reviews·Fabio ParmeggianiNicholas J Turner
May 23, 2019·The Analyst·Chuanpin ChenTingting Hong
Nov 17, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Evelin Sánta-BellLászló Poppe
Dec 2, 2017·Chembiochem : a European Journal of Chemical Biology·Pál CsukaLászló Poppe
May 7, 2020·International Journal of Molecular Sciences·Loredano PollegioniGianluca Molla
Aug 28, 2020·Frontiers in Bioengineering and Biotechnology·Sergio Martínez-RodríguezEsperanza Ortega
Nov 5, 2019·Trends in Plant Science·Jaime Barros, Richard A Dixon
May 30, 2019·Organic Letters·Rajendraprasad KotagiriQian Cai

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