Engineering a dirhodium artificial metalloenzyme for selective olefin cyclopropanation

Srivastava, Poonam; Yang, Hao; Ellis‐Guardiola, Ken; Lewis, Jared C.

doi:10.1038/ncomms8789

Cited by 190 publications

(180 citation statements)

References 53 publications

(77 reference statements)

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“…[167] As another example of de novo design, the use of a covalently linked di-rhodium catalyst within an optimised prolyl oligopeptidase resulted in an artificial metalloenzyme able to catalyse an olefin cyclopropanation. [168] A similar result was achieved in the artificial design of a copper binding site in a thermostable protein scaffold. Knowledge of both the requirements of ligating residues in the protein scaffold (a) (b) Fig.…”

Section: Engineering Metalloenzymes For Novel Functions Using Lessonssupporting

confidence: 49%

The Evolution of New Catalytic Mechanisms for Xenobiotic Hydrolysis in Bacterial Metalloenzymes

et al. 2016

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An increasing number of bacterial metalloenzymes have been shown to catalyse the breakdown of xenobiotics in the environment, while others exhibit a variety of promiscuous xenobiotic-degrading activities. Several different evolutionary processes have allowed these enzymes to gain or enhance xenobiotic-degrading activity. In this review, we have surveyed the range of xenobiotic-degrading metalloenzymes, and discuss the molecular and catalytic basis for the development of new activities. We also highlight how our increased understanding of the natural evolution of xenobiotic-degrading metalloenzymes can be been applied to laboratory enzyme design.

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Section: Engineering Metalloenzymes For Novel Functions Using Lessonssupporting

confidence: 49%

The Evolution of New Catalytic Mechanisms for Xenobiotic Hydrolysis in Bacterial Metalloenzymes

et al. 2016

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“…Protein scaffolds vary from CYP enzymes 75,78 to myoglobins 79 and other natural metalloenzymes 80 . The assembly of such novel catalytic entities occurred via the replacement of the natural cofactor, affinity tag technology or covalent linkage 80,81 . The Ward group has developed novel metalloenzymes using biotin-streptavidin technology.…”

Section: Novel Chemistries and Other Trendsmentioning

confidence: 99%

Opportunities and challenges for combining chemo- and biocatalysis

et al. 2018

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N ature has evolved highly efficient systems in the form of cascade reactions, which assemble the metabolic networks that support life (growth and survival). The basic principle of cascade reactions is also frequently used in biocatalysis, using enzymes in isolation, as well as in combination with chemocatalysts (see Fig. 1 and Box 1 for definition of terms) [1][2][3][4][5][6][7] . As there is no need for purification and isolation of intermediates, operating time, production costs and waste are reduced, and concomitantly, overall yields are improved. In addition, the problem of unstable or difficult to handle intermediates can be overcome, and reactivity as well as selectivity can be enhanced by avoiding unfavourable reaction equilibria through the cooperative effects of multiple catalysts 8 . Starting in the 1980s, the early examples of the combination of chemo-and biocatalysts were reported by the van Bekkum group, who pioneered the development of a process to make the sugar substitute d-mannitol from readily available d-glucose through the combination of a heterogeneous metal-catalysed hydrogenation and an enzyme-catalysed isomerization 9 . The first broadly applied technology for the combination of enzyme and metalcatalysts, which was the research subject of many academic groups as well as industry, emerged in the 1990s from the Williams group 10,11 and aimed to achieve higher yields than classical kinetic resolution of racemates, thus overcoming the limitation of a maximum yield of 50% in the latter case. A prominent example of work that developed this theme is the combination of lipase-catalysed kinetic resolution via acylation of secondary alcohols with Pd-or Rh-catalysed racemization via reversible transfer hydrogenation to achieve a dynamic kinetic resolution (DKR) [12][13][14] . This example was facilitated in part because lipases are active and stable in organic solvents. Later, for instance, Turner's group combined a monoamine oxidase-catalysed imine formation with a chemical reduction 15 to achieve the 100% theoretical yield through a deracemization process. In addition to the combination of metalcatalysis with enzymes, organocatalysis, electrochemistry and light-induced reaction couples have since then been studied extensively, going far beyond the scope of a DKR.The challenges to combining chemo-and biocatalysis in cascades (see Box 1 for definitions and Table 1) can be daunting, not least the requirement for the chemical step to occur in the presence of water, the preferred solvent for enzymes 3 . This Review therefore highlights recent examples of the combination of chemo-and biocatalysts in aqueous multistep syntheses, and looks at how to overcome limitations by, for example, design of appropriate reaction conditions, protein engineering and advanced reactor concepts. Furthermore, trends such as the integration of transition metalcatalysis into microorganisms and the introduction of novel chemistry into engineered enzymes are discussed, and a critical assessment of the impact of this research ...

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“…In addition to catalyzing intramolecular reactions with unactivated C-H bonds, Ir(Me)-CYP119-Max catalyzes intermolecular carbene insertion into a C-H bond. This reaction is challenging because the metal-carbene intermediate can undergo competitive diazo coupling or insert the carbene unit into the O-H bond of water (21,22). In fact, the model reaction between phthalan (10) and ethyl diazoacetate (EDA) forms alkene and alcohol as the dominant products when catalyzed by the For the ultimate goal of applying artificial metalloenzymes to the synthesis of organic molecules for fine chemicals, the reactions conducted by such catalytic systems should occur on preparative scales with high substrate concentrations, and the enzyme should react with high TONs and be amenable to attachment to a solid support for recycling.…”

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confidence: 99%

An artificial metalloenzyme with the kinetics of native enzymes

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et al. 2016

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Natural enzymes contain highly evolved active sites that lead to fast rates and high selectivities. Although artificial metalloenzymes have been developed that catalyze abiological transformations with high stereoselectivity, the activities of these artificial enzymes are much lower than those of natural enzymes. Here, we report a reconstituted artificial metalloenzyme containing an iridium porphyrin that exhibits kinetic parameters similar to those of natural enzymes. In particular, variants of the P450 enzyme CYP119 containing iridium in place of iron catalyze insertions of carbenes into C-H bonds with up to 98% enantiomeric excess, 35,000 turnovers, and 2550 hours −1 turnover frequency. This activity leads to intramolecular carbene insertions into unactivated C-H bonds and intermolecular carbene insertions into C-H bonds. These results lift the restrictions on merging chemical catalysis and biocatalysis to create highly active, productive, and selective metalloenzymes for abiological reactions.

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Engineering a dirhodium artificial metalloenzyme for selective olefin cyclopropanation

Cited by 190 publications

References 53 publications

The Evolution of New Catalytic Mechanisms for Xenobiotic Hydrolysis in Bacterial Metalloenzymes

The Evolution of New Catalytic Mechanisms for Xenobiotic Hydrolysis in Bacterial Metalloenzymes

Opportunities and challenges for combining chemo- and biocatalysis

An artificial metalloenzyme with the kinetics of native enzymes

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