Regioselective <i>para</i>‐Carboxylation of Catechols with a Prenylated Flavin Dependent Decarboxylase

Payer, Stefan E.; Marshall, S.A.; Bärland, Natalie; Sheng, Xiang; Reiter, Tamara; Đordić, Anđela; Steinkellner, Georg; Wuensch, Christiane; Kaltwasser, Susann; Fisher, Karl; Rigby, Stephen E. J.; Macheroux, Peter; Vonck, Janet; Gruber, Karl; Faber, Kurt; Himo, Fahmi; Leys, D.; Pavkov‐Keller, Tea; Glueck, Silvia M.

doi:10.1002/anie.201708091

Cited by 68 publications

(127 citation statements)

References 48 publications

(35 reference statements)

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“…2 A ). The distantly related AroY also exhibits rapid loss of activity, but only when incubated under aerobic conditions ( 13 ). However, when Fdc1 is incubated in the dark, activity remains constant for many hours, even under aerobic conditions.…”

Section: Resultsmentioning

confidence: 99%

The role of conserved residues in Fdc decarboxylase in prenylated flavin mononucleotide oxidative maturation, cofactor isomerization, and catalysis

Bailey

Payne

Fisher

et al. 2018

Journal of Biological Chemistry

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The UbiD family of reversible decarboxylases act on aromatic, heteroaromatic, and unsaturated aliphatic acids and utilize a prenylated flavin mononucleotide (prFMN) as cofactor, bound adjacent to a conserved Glu–Arg–Glu/Asp ionic network in the enzyme's active site. It is proposed that UbiD activation requires oxidative maturation of the cofactor, for which two distinct isomers, prFMNketimine and prFMNiminium, have been observed. It also has been suggested that only the prFMNiminium form is relevant to catalysis, which requires transient cycloaddition between substrate and cofactor. Using Aspergillus niger Fdc1 as a model system, we reveal that isomerization of prFMNiminium to prFMNketimine is a light-dependent process that is largely independent of the Glu277–Arg173–Glu282 network and accompanied by irreversible loss of activity. On the other hand, efficient catalysis was highly dependent on an intact Glu–Arg–Glu network, as only Glu → Asp substitutions retain activity. Surprisingly, oxidative maturation to form the prFMNiminium species is severely affected only for the R173A variant. In summary, the unusual irreversible isomerization of prFMN is light-dependent and probably proceeds via high-energy intermediates but is independent of the Glu–Arg–Glu network. Our results from mutagenesis, crystallographic, spectroscopic, and kinetic experiments indicate a clear role for the Glu–Arg–Glu network in both catalysis and oxidative maturation.

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Section: Resultsmentioning

confidence: 99%

The role of conserved residues in Fdc decarboxylase in prenylated flavin mononucleotide oxidative maturation, cofactor isomerization, and catalysis

Bailey

Payne

Fisher

et al. 2018

Journal of Biological Chemistry

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“…25,27 FDC enzymatic activity requires oxygen to form an active prFMN form; however, more oxygen exposure leads to irreversible oxidative maturation to form an inactive form. 28,29 Therefore, in this pathway, anaerobic conditions are suitable for prFMN activation and ccMA production because oxygen is required for catechol ring opening by catA, while anaerobic conditions are needed to maintain FDC activity. To meet these requirements, cultivation of 1,3-butadiene-producing strains under microaerobic conditions is done.…”

Section: Discussionmentioning

confidence: 99%

“…Intermediate substrates (ccMA and PA) remain in the medium at the end of fermentation because of the antinomy that prFMN-containing FMN requires oxygen to activate prFMN only once, while more oxygen exposure leads to irreversible inactivation of activated prFMN. 28,29 In addition, the intermediate compound PA shows cellular toxicity. Supplementary Fig.…”

Section: Discussionmentioning

confidence: 99%

“…26 The prFMN-containing FDC can recognize aromatic compounds and α,β-unsaturated carboxylic acids without aromatic rings. 27,28,29,30,31,32,33 FDC can decarboxylate hexadienoic acid, whose structure is very similar to ccMA. 25 Therefore, we hypothesized that by designing a substrate-binding site of FDC to change substrate speci city, FDC could recognize ccMA.…”

Section: Introductionmentioning

confidence: 99%

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Direct 1,3-butadiene biosynthesis in Escherichia coli via a tailored ferulic acid decarboxylase mutant

Mori

Noda

Shirai

et al. 2020

Preprint

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The C4 unsaturated compound 1,3-butadiene is an important monomer in synthetic rubber and engineering plastic production. However, microorganisms cannot directly produce 1,3-butadiene using glucose as a renewable carbon source via biological processes. This study constructed a novel artificial metabolic pathway for 1,3-butadiene production from glucose in Escherichia coli by combining the cis,cis-muconic acid (ccMA)-producing pathway and tailored ferulic acid decarboxylase mutants. The rational enzyme design of the substrate-binding site by computational simulation improved 1,3-butadiene-producing ccMA decarboxylation with a small mutant library. We found that changing dissolved oxygen and controlling pH were important factors for 1,3-butadiene production. Using dissolved oxygen–stat fed-batch fermentation in a 1-L jar fermenter, we could produce 2.1 g L− 1 of 1,3-butadiene. These results indicated that using a rational enzyme design, we can produce unnatural/nonbiological compounds (those that are made from petroleum and cannot be produced by microorganisms) using glucose as a renewable carbon source.

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“…8-Formyl-FAD (8-fFADH) appeared to be the native cofactor in formate oxidase (FOX) [40]. A flavin-N5-oxide cofactor was encountered in EncM [41], while a prenylated form of FMN (prFMN) was found in (de)carboxylases (Figure 6b) [42].…”

Section: Naturally Occurring Flavin Derivativesmentioning

confidence: 99%

Alternative coenzymes for biocatalysis

Guarneri

Berkel

Paul

2019

Current Opinion in Biotechnology

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Coenzymes are ubiquitous in Nature, assisting in enzymecatalysed reactions. Several coenzymes, nicotinamides and flavins, have been known for close to a century, whereas variations of those organic molecules have more recently come to light. In general, the requirement of these coenzymes imposes certain constraints for in vitro enzyme use in biocatalytic processes. Alternative coenzymes have risen to circumvent the cost factor, tune reaction rates or obtain different chemical reactivity. This review will focus on these alternatives and their role and applications in biocatalysis.

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Regioselective para‐Carboxylation of Catechols with a Prenylated Flavin Dependent Decarboxylase

Cited by 68 publications

References 48 publications

The role of conserved residues in Fdc decarboxylase in prenylated flavin mononucleotide oxidative maturation, cofactor isomerization, and catalysis

The role of conserved residues in Fdc decarboxylase in prenylated flavin mononucleotide oxidative maturation, cofactor isomerization, and catalysis

Direct 1,3-butadiene biosynthesis in Escherichia coli via a tailored ferulic acid decarboxylase mutant

Alternative coenzymes for biocatalysis

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