Enzymatic construction of highly strained carbocycles

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Abstract

Small carbocycles are structurally rigid and possess high intrinsic energy due to their significant ring strain. These unique features lead to broad applications, but also create challenges for their construction. We report the discovery and engineering of hemeproteins that catalyze the formation of chiral bicyclobutanes, one of the most strained four-membered systems, via successive carbene addition to unsaturated carbon–carbon bonds. Enzymes that produce cyclopropenes, putative intermediates to the bicyclobutanes, were also identified. These genetically-encoded proteins are readily optimized by directed evolution, function in Escherichia coli, and act on structurally diverse substrates with high efficiency and selectivity, providing an effective route to many chiral strained structures. This biotransformation is easily performed on preparative scale and the resulting strained carbocycles can be derivatized, opening myriad potential applications. Heme enzymes engineered by directed evolution catalyze the asymmetric formation of highly strained bicyclobutanes and cyclopropenes.

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Most cited references 55

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A perspective on enzyme catalysis.

Stephen J. Benkovic, Sharon Hammes-Schiffer (2003)

The seminal hypotheses proposed over the years for enzymatic catalysis are scrutinized. The historical record is explored from both biochemical and theoretical perspectives. Particular attention is given to the impact of molecular motions within the protein on the enzyme's catalytic properties. A case study for the enzyme dihydrofolate reductase provides evidence for coupled networks of predominantly conserved residues that influence the protein structure and motion. Such coupled networks have important implications for the origin and evolution of enzymes, as well as for protein engineering.

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Record: found
Abstract: found
Article: not found

Directed evolution of cytochrome c for carbon-silicon bond formation: Bringing silicon to life.

S. B. Jennifer Kan, Russell D Lewis, Kai Chen … (2016)

Enzymes that catalyze carbon-silicon bond formation are unknown in nature, despite the natural abundance of both elements. Such enzymes would expand the catalytic repertoire of biology, enabling living systems to access chemical space previously only open to synthetic chemistry. We have discovered that heme proteins catalyze the formation of organosilicon compounds under physiological conditions via carbene insertion into silicon-hydrogen bonds. The reaction proceeds both in vitro and in vivo, accommodating a broad range of substrates with high chemo- and enantioselectivity. Using directed evolution, we enhanced the catalytic function of cytochrome c from Rhodothermus marinus to achieve more than 15-fold higher turnover than state-of-the-art synthetic catalysts. This carbon-silicon bond-forming biocatalyst offers an environmentally friendly and highly efficient route to producing enantiopure organosilicon molecules.

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Record: found
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Article: not found

Simultaneous determination of hemes a, b, and c from pyridine hemochrome spectra.

E A Berry, B L Trumpower (1987)

Two procedures for analyzing overlapping optical spectra of mixtures of pyridine hemochromes are described, and extinction coefficients of pyridine hemochromes are provided for use with these methods. In the first procedure, absorbance is measured at a number of wavelengths equal to the number of components to be analyzed. This is the minimum amount of spectral data from which the concentration of each species can be calculated. In the second procedure, absorbance is measured at a number of wavelengths greater than the number of components to be analyzed. This redundancy of information makes it impossible to fit spectra which contain contributions from additional components, unless the spectra of the additional components are equal to linear combinations of the spectra of the species being analyzed. These two procedures are generally applicable to analyses of absolute or difference spectra of mixtures of components obeying Beer's law. The sensitivity to error in the absorbance measurements is only slightly greater than that for measuring a pure component at a single wavelength.