Oxidative Enzymatic Alkene Cleavage: Indications for a Nonclassical Enzyme Mechanism

Lara, Miguel; Mutti, Francesco G.; Glueck, Silvia M.; Kroutil, Wolfgang

doi:10.1021/ja8097096

Cited by 40 publications

(18 citation statements)

References 31 publications

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“…Continuing our previous studies on enzymatic alkene cleavage by using the fungus Trametes hirsuta, [20,21] we noticed by serendipity that peroxidases [22] cleave the C=C double bond of t-anethole in the presence of molecular oxygen as the main reaction (Scheme 1). It has to be noted, that the previously observed alkene cleavage by Trametes hirsuta did not result from a peroxidase.…”

Section: Introductionsupporting

confidence: 72%

Ostensible Enzyme Promiscuity: Alkene Cleavage by Peroxidases

Mutti

Lara

Kroutil

et al. 2010

Chemistry A European J

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Enzyme promiscuity is generally accepted as the ability of an enzyme to catalyse alternate chemical reactions besides the 'natural' one. In this paper peroxidases were shown to catalyse the cleavage of a C=C double bond adjacent to an aromatic moiety for selected substrates at the expense of molecular oxygen at an acidic pH. It was clearly shown that the reaction occurs due to the presence of the enzyme; furthermore, the reactivity was clearly linked to the hemin moiety of the peroxidase. Comparison of the transformations catalysed by peroxidase and by hemin chloride revealed that these two reactions proceed equally fast; additional experiments confirmed that the peptide backbone was not obligatory for the reaction and only a single functional group of the enzyme was required, namely in this case the prosthetic group (hemin). Consequently, we propose to define such a promiscuous activity as 'ostensible enzyme promiscuity'. Thus, we call an activity that is catalysed by an enzyme 'ostensible enzyme promiscuity' if the reactivity can be tracked back to a single catalytic site, which on its own can already perform the reaction equally well in the absence of the peptide backbone.

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Section: Introductionsupporting

confidence: 72%

Ostensible Enzyme Promiscuity: Alkene Cleavage by Peroxidases

Mutti

Lara

Kroutil

et al. 2010

Chemistry A European J

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“…Mechanic investigations reveal that the new biocatalyst follows neither the standard dioxygenase nor the monooxygenase mechanism. It instead seems to prefer a mechanism akin to a 2 + 2 cycloaddition, as two oxygen atoms derived from two different molecules of dioxygen are incorporated into the carbonyl products (Figure 8) (70). Very recently, this new biocatalyst was identified as a novel Mn 3+ -containing proteinase A analog, in which Mn 3+ is uniquely bound to oxygen ligands only (71).…”

Section: Alkene Oxidases (Ozonidases)mentioning

confidence: 99%

Biocatalysis: A Status Report

Bommarius

2015

Annu. Rev. Chem. Biomol. Eng.

136

101

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This review describes the status of the fields of biocatalysts and enzymes, as well as existing drawbacks, and recent advances in the areas deemed to represent drawbacks. Although biocatalysts are often highly active and extremely selective, there are still drawbacks associated with biocatalysis as a generally applicable technique: the lack of designability of biocatalysts; their limits of stability; and the insufficient number of well-characterized, ready-to-use biocatalysts. There has been significant progress on the following fronts: (a) novel protein engineering tools, both experimental and computational, have significantly enhanced the toolbox for biocatalyst development. (b) The deactivation of biocatalysts under various stresses can be described quantitatively via rational models. There are several cases of spectacular leaps of stabilization after accumulating all stabilizing mutations found in earlier rounds. The concept that stabilization against one type of stress commonly also stabilizes against other types of stress is now experimentally considerably better founded than a few years ago.

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“…Conversely, enzymes can activate the most innocuous oxidant, that is, molecular oxygen, and catalyse the alkene cleavage at ambient temperature and atmospheric pressure in aqueous buffer. Besides, in certain cases enzymes are capable to cleave olefinic functionalities in high chemo- and regioselective fashion allowing biocatalysis to compete with chemical methods [7–9]. …”

Section: Introductionmentioning

confidence: 99%

Alkene Cleavage Catalysed by Heme and Nonheme Enzymes: Reaction Mechanisms and Biocatalytic Applications

Mutti

2012

Bioinorganic Chemistry and Applications

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The oxidative cleavage of alkenes is classically performed by chemical methods, although they display several drawbacks. Ozonolysis requires harsh conditions (−78°C, for a safe process) and reducing reagents in a molar amount, whereas the use of poisonous heavy metals such as Cr, Os, or Ru as catalysts is additionally plagued by low yield and selectivity. Conversely, heme and nonheme enzymes can catalyse the oxidative alkene cleavage at ambient temperature and atmospheric pressure in an aqueous buffer, showing excellent chemo- and regioselectivities in certain cases. This paper focuses on the alkene cleavage catalysed by iron cofactor-dependent enzymes encompassing the reaction mechanisms (in case where it is known) and the application of these enzymes in biocatalysis.

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Oxidative Enzymatic Alkene Cleavage: Indications for a Nonclassical Enzyme Mechanism

Cited by 40 publications

References 31 publications

Ostensible Enzyme Promiscuity: Alkene Cleavage by Peroxidases

Ostensible Enzyme Promiscuity: Alkene Cleavage by Peroxidases

Biocatalysis: A Status Report

Alkene Cleavage Catalysed by Heme and Nonheme Enzymes: Reaction Mechanisms and Biocatalytic Applications

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