Cofactor promiscuity among F 420-dependent reductases enables them to catalyse both oxidation and reduction of the same substrate

Gauri V. Lapalikar; Matthew C. Taylor; Andrew C. Warden; Hideki Onagi; James E. Hennessy; Roger J. Mulder; Colin Scott; Susan E. Brown; Robyn J. Russell; Chris J. Easton; John G. Oakeshott

doi:10.1039/c2cy20129a

Cofactor promiscuity among F ₄₂₀-dependent reductases enables them to catalyse both oxidation and reduction of the same substrate

Gauri V. Lapalikar, Matthew C. Taylor^*, Andrew C. Warden, Hideki Onagi, James E. Hennessy, Roger J. Mulder, Colin Scott, Susan E. Brown, Robyn J. Russell, Chris J. Easton, John G. Oakeshott

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

17 Citations (Scopus)

Abstract

The recently reported F ₄₂₀H ₂-dependent reductases (FDRs) catalyse the reduction of aflatoxins and coumarin via hydrogenation of the α,β-unsaturated moiety. We report that three FDRs (MSMEG-2027, MSMEG-6848 and MSMEG-3356) from Mycobacterium smegmatis also exhibit a different catalytic function towards some aflatoxins through the use of a different cofactor. When F ₄₂₀ was replaced by FMN in these three enzymes, the aflatoxins AFG1 and AFG2 were oxidised via dehydrogenation, producing the reduced cofactor (FMNH ₂) and an unstable aflatoxin derivative that hydrolyses to an enol with three distinct structural isomers. Both the oxidation and reduction reactions are discussed in detail. This is the first example of an enzyme showing promiscuity for its cofactor leading to divergence of function against the same substrate.

Original language	English
Pages (from-to)	1560-1567
Number of pages	8
Journal	Catalysis Science and Technology
Volume	2
Issue number	8
DOIs	https://doi.org/10.1039/c2cy20129a
Publication status	Published - Aug 2012

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Lapalikar, G. V., Taylor, M. C., Warden, A. C., Onagi, H., Hennessy, J. E., Mulder, R. J., Scott, C., Brown, S. E., Russell, R. J., Easton, C. J., & Oakeshott, J. G. (2012). Cofactor promiscuity among F ₄₂₀-dependent reductases enables them to catalyse both oxidation and reduction of the same substrate. Catalysis Science and Technology, 2(8), 1560-1567. https://doi.org/10.1039/c2cy20129a

@article{6edcb39eff2744d791ce194fc8f7e4d3,

title = "Cofactor promiscuity among F 420-dependent reductases enables them to catalyse both oxidation and reduction of the same substrate",

abstract = "The recently reported F 420H 2-dependent reductases (FDRs) catalyse the reduction of aflatoxins and coumarin via hydrogenation of the α,β-unsaturated moiety. We report that three FDRs (MSMEG-2027, MSMEG-6848 and MSMEG-3356) from Mycobacterium smegmatis also exhibit a different catalytic function towards some aflatoxins through the use of a different cofactor. When F 420 was replaced by FMN in these three enzymes, the aflatoxins AFG1 and AFG2 were oxidised via dehydrogenation, producing the reduced cofactor (FMNH 2) and an unstable aflatoxin derivative that hydrolyses to an enol with three distinct structural isomers. Both the oxidation and reduction reactions are discussed in detail. This is the first example of an enzyme showing promiscuity for its cofactor leading to divergence of function against the same substrate.",

author = "Lapalikar, {Gauri V.} and Taylor, {Matthew C.} and Warden, {Andrew C.} and Hideki Onagi and Hennessy, {James E.} and Mulder, {Roger J.} and Colin Scott and Brown, {Susan E.} and Russell, {Robyn J.} and Easton, {Chris J.} and Oakeshott, {John G.}",

year = "2012",

month = aug,

doi = "10.1039/c2cy20129a",

language = "English",

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pages = "1560--1567",

journal = "Catalysis Science and Technology",

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publisher = "Royal Society of Chemistry",

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}

Lapalikar, GV, Taylor, MC, Warden, AC, Onagi, H, Hennessy, JE, Mulder, RJ, Scott, C, Brown, SE, Russell, RJ, Easton, CJ & Oakeshott, JG 2012, 'Cofactor promiscuity among F ₄₂₀-dependent reductases enables them to catalyse both oxidation and reduction of the same substrate', Catalysis Science and Technology, vol. 2, no. 8, pp. 1560-1567. https://doi.org/10.1039/c2cy20129a

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T1 - Cofactor promiscuity among F 420-dependent reductases enables them to catalyse both oxidation and reduction of the same substrate

AU - Lapalikar, Gauri V.

AU - Taylor, Matthew C.

AU - Warden, Andrew C.

AU - Onagi, Hideki

AU - Hennessy, James E.

AU - Mulder, Roger J.

AU - Scott, Colin

AU - Brown, Susan E.

AU - Russell, Robyn J.

AU - Easton, Chris J.

AU - Oakeshott, John G.

PY - 2012/8

Y1 - 2012/8

N2 - The recently reported F 420H 2-dependent reductases (FDRs) catalyse the reduction of aflatoxins and coumarin via hydrogenation of the α,β-unsaturated moiety. We report that three FDRs (MSMEG-2027, MSMEG-6848 and MSMEG-3356) from Mycobacterium smegmatis also exhibit a different catalytic function towards some aflatoxins through the use of a different cofactor. When F 420 was replaced by FMN in these three enzymes, the aflatoxins AFG1 and AFG2 were oxidised via dehydrogenation, producing the reduced cofactor (FMNH 2) and an unstable aflatoxin derivative that hydrolyses to an enol with three distinct structural isomers. Both the oxidation and reduction reactions are discussed in detail. This is the first example of an enzyme showing promiscuity for its cofactor leading to divergence of function against the same substrate.

AB - The recently reported F 420H 2-dependent reductases (FDRs) catalyse the reduction of aflatoxins and coumarin via hydrogenation of the α,β-unsaturated moiety. We report that three FDRs (MSMEG-2027, MSMEG-6848 and MSMEG-3356) from Mycobacterium smegmatis also exhibit a different catalytic function towards some aflatoxins through the use of a different cofactor. When F 420 was replaced by FMN in these three enzymes, the aflatoxins AFG1 and AFG2 were oxidised via dehydrogenation, producing the reduced cofactor (FMNH 2) and an unstable aflatoxin derivative that hydrolyses to an enol with three distinct structural isomers. Both the oxidation and reduction reactions are discussed in detail. This is the first example of an enzyme showing promiscuity for its cofactor leading to divergence of function against the same substrate.

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JF - Catalysis Science and Technology

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Cofactor promiscuity among F ₄₂₀-dependent reductases enables them to catalyse both oxidation and reduction of the same substrate

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