The taming of oxygen: biocatalytic oxyfunctionalisations

Holtmann, Dirk; Fraaije, Marco W.; Arends, Isabel W. C. E.; Opperman, Diederik J.; Hollmann, Frank

doi:10.1039/c3cc49747j

Cited by 105 publications

(90 citation statements)

References 313 publications

(197 reference statements)

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“…Oxygenases, which catalyze the addition of oxygen atoms into many organic compounds, show a remarkable enantio- and regio-selectivity and broad substrate specificity [7,8,9,10]. These features make them valuable biocatalysts for the production of synthons relevant for pharmaceutical and chemical industries [4], and it has been suggested that the use of these enzymes will be as prominent as the well-established hydrolases and dehydrogenases [7].…”

Section: Introductionmentioning

confidence: 99%

“…These features make them valuable biocatalysts for the production of synthons relevant for pharmaceutical and chemical industries [4], and it has been suggested that the use of these enzymes will be as prominent as the well-established hydrolases and dehydrogenases [7]. Furthermore, their application in chemical synthesis can replace the use of potentially harmful chemicals (i.e., green chemistry) [8].…”

Section: Introductionmentioning

confidence: 99%

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Prospecting Biotechnologically-Relevant Monooxygenases from Cold Sediment Metagenomes: An In Silico Approach

et al. 2017

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The goal of this work was to identify sequences encoding monooxygenase biocatalysts with novel features by in silico mining an assembled metagenomic dataset of polar and subpolar marine sediments. The targeted enzyme sequences were Baeyer–Villiger and bacterial cytochrome P450 monooxygenases (CYP153). These enzymes have wide-ranging applications, from the synthesis of steroids, antibiotics, mycotoxins and pheromones to the synthesis of monomers for polymerization and anticancer precursors, due to their extraordinary enantio-, regio-, and chemo- selectivity that are valuable features for organic synthesis. Phylogenetic analyses were used to select the most divergent sequences affiliated to these enzyme families among the 264 putative monooxygenases recovered from the ~14 million protein-coding sequences in the assembled metagenome dataset. Three-dimensional structure modeling and docking analysis suggested features useful in biotechnological applications in five metagenomic sequences, such as wide substrate range, novel substrate specificity or regioselectivity. Further analysis revealed structural features associated with psychrophilic enzymes, such as broader substrate accessibility, larger catalytic pockets or low domain interactions, suggesting that they could be applied in biooxidations at room or low temperatures, saving costs inherent to energy consumption. This work allowed the identification of putative enzyme candidates with promising features from metagenomes, providing a suitable starting point for further developments.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Prospecting Biotechnologically-Relevant Monooxygenases from Cold Sediment Metagenomes: An In Silico Approach

et al. 2017

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“…A number of other types of enzyme in this class have also been subject to significant interest as biocatalysts because of their ability to functionalise inert C-H bonds. 115,[272][273][274][275] A number of recent reviews have extensively discussed these enzymes both in terms of structural biology and their applications as biocatalysts. 115,116,[275][276][277] This review will discuss how the methods employed to allow the application of some of these enzymes as industrial biocatalysts might be applied to improve the viability of using flavin-dependent halogenases in the same way.…”

Section: Natural Occurrence and Mechanism Of Flavin-dependent Monooxymentioning

confidence: 99%

“…272,275 Reduced flavin co-factors, required by all enzymes of this class, are unstable with respect to oxygen.…”

Section: Flavin-dependent Monooxygenases As Biocatalystsmentioning

confidence: 99%

Development of Halogenase Enzymes for Use in Synthesis

Latham

Brandenburger

Shepherd³

et al. 2017

Chem. Rev.

285

244

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Nature has evolved halogenase enzymes to regioselectively halogenate a diverse range of biosynthetic precursors, with the halogens introduced often having a profound effect on the biological activity of the resulting natural products. Synthetic endeavours to create non-natural bioactive small molecules for pharmaceutical and agrochemical applications have also arrived at a similar conclusion -halogens can dramatically improve the properties of organic molecules for selective modulation of biological targets in vivo. Consequently a high proportion of pharmaceuticals and agrochemicals on the market today possess halogens. Halogenated organic compounds are also common intermediates in synthesis and are particularly valuable in metal catalyzed cross-coupling reactions.Despite the potential utility of organohalogens, traditional non-enzymatic halogenation chemistry utilizes deleterious reagents and often lacks regiocontrol. Reliable, facile and cleaner methods for the regioselective halogenation of organic compounds are therefore essential in the development of economical and environmentally-friendly industrial processes. A potential avenue towards such methods is the use of halogenase enzymes, responsible for the biosynthesis of halogenated natural products, as biocatalysts. This review will discuss the advances towards this goal thus far, in addition to untapped potential sources of such biocatalysts and how further development of the enzymes may be focused in order to achieve the goal of industrial scale biohalogenation.

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“…In this context, enzyme catalysis represents a still not fully exploited potential for the development of sustainable and 'greener' chemistry 1 . Oxidoreductases have the capacity to catalyze the introduction and modification of functional groups under mild reactions conditions and belong to the most important biocatalysts 2 . Most redox transformations require the supply of external of cofactors such as NAD(P)H. Methods for cofactor regeneration have been applied in industrial scale.…”

Section: Introductionmentioning

confidence: 99%

Light-driven Enzymatic Decarboxylation

Köninger

Grote

Zachos

et al. 2016

JoVE

Self Cite

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Oxidoreductases belong to the most-applied industrial enzymes. Nevertheless, they need external electrons whose supply is often costly and challenging. Recycling of the electron donors NADH or NADPH requires the use of additional enzymes and sacrificial substrates. Interestingly, several oxidoreductases accept hydrogen peroxide as electron donor. While being inexpensive, this reagent often reduces the stability of enzymes. A solution to this problem is the in situ generation of the cofactor. The continuous supply of the cofactor at low concentration drives the reaction without impairing enzyme stability. This paper demonstrates a method for the light-catalyzed in situ generation of hydrogen peroxide with the example of the heme-dependent fatty acid decarboxylase OleT JE . The fatty acid decarboxylase OleT JE was discovered due to its unique ability to produce long-chain 1-alkenes from fatty acids, a hitherto unknown enzymatic reaction. 1-alkenes are widely used additives for plasticizers and lubricants. OleT JE has been shown to accept electrons from hydrogen peroxide for the oxidative decarboxylation. While addition of hydrogen peroxide damages the enzyme and results in low yields, in situ generation of the cofactor circumvents this problem. The photobiocatalytic system shows clear advantages regarding enzyme activity and yield, resulting in a simple and efficient system for fatty acid decarboxylation.

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The taming of oxygen: biocatalytic oxyfunctionalisations

Abstract: The scope and limitations of oxygenases as catalysts for preparative organic synthesis is discussed.

Cited by 105 publications

References 313 publications

Prospecting Biotechnologically-Relevant Monooxygenases from Cold Sediment Metagenomes: An In Silico Approach

Prospecting Biotechnologically-Relevant Monooxygenases from Cold Sediment Metagenomes: An In Silico Approach

Development of Halogenase Enzymes for Use in Synthesis

Light-driven Enzymatic Decarboxylation

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