Exploring the substrate scope of ferulic acid decarboxylase (FDC1) from Saccharomyces cerevisiae

Emma Zsófia Aletta Nagy, Csaba Levente Nagy, Alina Filip, Katalin Nagy, Emese Gál, Róbert Tőtős, L. Poppe, Csaba Paizs, László Csaba Bencze

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Ferulic acid decarboxylase from Saccharomyces cerevisiae (ScFDC1) was described to possess a novel, prenylated flavin mononucleotide cofactor (prFMN) providing the first enzymatic 1,3-dipolar cycloaddition mechanism. The high tolerance of the enzyme towards several non-natural substrates, combined with its high quality, atomic resolution structure nominates FDC1 an ideal candidate as flexible biocatalyst for decarboxylation reactions leading to synthetically valuable styrenes. Herein the substrate scope of ScFDC1 is explored on substituted cinnamic acids bearing different functional groups (–OCH3, –CF3 or –Br) at all positions of the phenyl ring (o−, m−, p−), as well as on several biaryl and heteroaryl cinnamic acid analogues or derivatives with extended alkyl chain. It was found that E. coli whole cells expressing recombinant ScFDC1 could transform a large variety of substrates with high conversion, including several bulky aryl and heteroaryl cinnamic acid analogues, that characterize ScFDC1 as versatile and highly efficient biocatalyst. Computational studies revealed energetically favoured inactive binding positions and limited active site accessibility for bulky and non-linear substrates, such as 2-phenylthiazol-4-yl-, phenothiazine-2-yl- and 5-(4-bromophenyl)furan-2-yl) acrylic acids. In accordance with the computational predictions, site-directed mutagenesis of residue I330 provided variants with catalytic activity towards phenothiazine-2-yl acrylic acid and provides a basis for altering the substrate specificity of ScFDC1 by structure based rational design.

Original languageEnglish
Article number647
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - Dec 1 2019

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Saccharomyces cerevisiae
Styrenes
Enzymes
Flavin Mononucleotide
Decarboxylation
Cycloaddition Reaction
Substrate Specificity
Site-Directed Mutagenesis
Catalytic Domain
Escherichia coli
cinnamic acid
phenylacrylic acid decarboxylase
phenothiazine
acrylic acid
furan

ASJC Scopus subject areas

  • General

Cite this

Nagy, E. Z. A., Nagy, C. L., Filip, A., Nagy, K., Gál, E., Tőtős, R., ... Bencze, L. C. (2019). Exploring the substrate scope of ferulic acid decarboxylase (FDC1) from Saccharomyces cerevisiae. Scientific Reports, 9(1), [647]. https://doi.org/10.1038/s41598-018-36977-x

Exploring the substrate scope of ferulic acid decarboxylase (FDC1) from Saccharomyces cerevisiae. / Nagy, Emma Zsófia Aletta; Nagy, Csaba Levente; Filip, Alina; Nagy, Katalin; Gál, Emese; Tőtős, Róbert; Poppe, L.; Paizs, Csaba; Bencze, László Csaba.

In: Scientific Reports, Vol. 9, No. 1, 647, 01.12.2019.

Research output: Contribution to journalArticle

Nagy, EZA, Nagy, CL, Filip, A, Nagy, K, Gál, E, Tőtős, R, Poppe, L, Paizs, C & Bencze, LC 2019, 'Exploring the substrate scope of ferulic acid decarboxylase (FDC1) from Saccharomyces cerevisiae', Scientific Reports, vol. 9, no. 1, 647. https://doi.org/10.1038/s41598-018-36977-x
Nagy, Emma Zsófia Aletta ; Nagy, Csaba Levente ; Filip, Alina ; Nagy, Katalin ; Gál, Emese ; Tőtős, Róbert ; Poppe, L. ; Paizs, Csaba ; Bencze, László Csaba. / Exploring the substrate scope of ferulic acid decarboxylase (FDC1) from Saccharomyces cerevisiae. In: Scientific Reports. 2019 ; Vol. 9, No. 1.
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