A Route to Novel Functional Metalloproteins via Hybrids of Cytochrome P450 and Cytochrome c

Ying, Tianlei; Zhong, Fangfang; Wang, Zhonghua; Li, Wei; Tan, Xiangshi; Huang, Zhong‐Xian

doi:10.1002/cbic.201000631

Cited by 8 publications

(6 citation statements)

References 21 publications

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“…Huang, Tan, and co-workers [61] explored this new approach to design hybrid proteins of cyt c and cyt P450 or peroxidase by genetic and protein engineering. Their aim was to create a novel type of heme protein with the superior stability of cyt c and the catalytic activity of cyt P450 or peroxidase.…”

Section: Protein Hybridizationmentioning

confidence: 99%

Rational Heme Protein Design: All Roads Lead to Rome

Lin

Sawyer

Wang

2013

Chemistry An Asian Journal

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Heme proteins are among the most abundant and important metalloproteins, exerting diverse biological functions including oxygen transport, small molecule sensing, selective CH bond activation, nitrite reduction, and electron transfer. Rational heme protein designs focus on the modification of the heme‐binding active site and the heme group, protein hybridization and domain swapping, and de novo design. These strategies not only provide us with unique advantages for illustrating the structure–property–reactivity–function (SPRF) relationship of heme proteins in nature but also endow us with the ability to create novel biocatalysts and biosensors.

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Section: Protein Hybridizationmentioning

confidence: 99%

Rational Heme Protein Design: All Roads Lead to Rome

Lin

Sawyer

Wang

2013

Chemistry An Asian Journal

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“…Their aim was to create a novel type of heme protein with the superior stability of cyt c and the catalytic activity of cyt P450 or peroxidase. In one study,61a the substrate recognition sites (SRSs) of cyt P450 were incorporated into the framework of cyt c using the gene overlap extension method. These hybrid proteins, termed HY1‐HY6, retain the stability of cyt c yet possess the catalytic activity of cyt P450 (both HY1 and HY6 were found to be capable of converting styrene into styrene oxide, with a yield of about 3 %, which is comparable to that achieved with CYP450; cyt c is not able to catalyze this reaction).…”

Section: Introductionmentioning

confidence: 99%

Operando Attenuated Total Reflectance FTIR Spectroscopy: Studies on the Different Selectivity Observed in Benzyl Alcohol Oxidation

et al. 2015

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Au, Pd, and AuPd supported on TiO2 were prepared by a sol immobilization route. Operando attenuated total reflectance (ATR) IR spectroscopy and catalytic batch reactor experiments were performed in parallel to elucidate the different catalytic performance of the catalysts in the liquid‐phase oxidation of benzyl alcohol. Pd/TiO2 exhibited a higher activity than AuPd/TiO2 and Au/TiO2, but the modification of Pd with Au demonstrated a significant stability enhancement. ATR‐IR spectroscopy evidenced that the presence of Au facilitates the desorption of byproducts, which thus reduces the extent of deactivation of the active sites caused by the irreversible adsorption of benzoate species. Although benzaldehyde was the main product in both catalysts, the nature of the byproducts differs. Pd/TiO2 favored the deoxygenation of benzyl alcohol to produce toluene as the main byproduct. Conversely, AuPd/TiO2 promoted the transformation of benzaldehyde to benzoic acid.

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“…Replacing these residues with key protein segments from other heme-containing enzymes that are responsible for substrate recognition and binding offers a great opportunity for protein engineering. In 2011, Ying et al reported a P450-mimetic system in C c by constructing hybrid proteins in which the segment of the coordination loop (residues 78–85) of yeast iso-1 C c was substituted by the “substrate recognition sites” (SRSs) of P450 (Figure b) . Two constructs, HY1 and HY2, which possess SRS-1 and SRS-2 of P450, respectively, were successfully expressed and further exhibited P450-like function by catalyzing the oxidation of styrene while maintaining the high stability of WT-C c .…”

Section: Catalysis Beyond the Primary Coordination Sphere By Heme Pro...mentioning

confidence: 99%

Designing Artificial Metalloenzymes by Tuning of the Environment beyond the Primary Coordination Sphere

et al. 2022

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Metalloenzymes catalyze a variety of reactions using a limited number of natural amino acids and metallocofactors. Therefore, the environment beyond the primary coordination sphere must play an important role in both conferring and tuning their phenomenal catalytic properties, enabling active sites with otherwise similar primary coordination environments to perform a diverse array of biological functions. However, since the interactions beyond the primary coordination sphere are numerous and weak, it has been difficult to pinpoint structural features responsible for the tuning of activities of native enzymes. Designing artificial metalloenzymes (ArMs) offers an excellent basis to elucidate the roles of these interactions and to further develop practical biological catalysts. In this review, we highlight how the secondary coordination spheres of ArMs influence metal binding and catalysis, with particular focus on the use of native protein scaffolds as templates for the design of ArMs by either rational design aided by computational modeling, directed evolution, or a combination of both approaches. In describing successes in designing heme, nonheme Fe, and Cu metalloenzymes, heteronuclear metalloenzymes containing heme, and those ArMs containing other metal centers (including those with non-native metal ions and metallocofactors), we have summarized insights gained on how careful controls of the interactions in the secondary coordination sphere, including hydrophobic and hydrogen bonding interactions, allow the generation and tuning of these respective systems to approach, rival, and, in a few cases, exceed those of native enzymes. We have also provided an outlook on the remaining challenges in the field and future directions that will allow for a deeper understanding of the secondary coordination sphere a deeper understanding of the secondary coordintion sphere to be gained, and in turn to guide the design of a broader and more efficient variety of ArMs.

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A Route to Novel Functional Metalloproteins via Hybrids of Cytochrome P450 and Cytochrome c

Cited by 8 publications

References 21 publications

Rational Heme Protein Design: All Roads Lead to Rome

Rational Heme Protein Design: All Roads Lead to Rome

Operando Attenuated Total Reflectance FTIR Spectroscopy: Studies on the Different Selectivity Observed in Benzyl Alcohol Oxidation

Designing Artificial Metalloenzymes by Tuning of the Environment beyond the Primary Coordination Sphere

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