3 publications

3 publications

Design of Artificial Metalloproteins/Metalloenzymes by Tuning Noncovalent Interactions

Review

Hirota, S.; Lin, Y.-W.

J. Biol. Inorg. Chem. 2018, 23, 7-25, 10.1007/s00775-017-1506-8

Noncovalent weak interactions [hydrophobic interaction and hydrogen (H)-bond] play crucial roles in controlling the functions of biomolecules, and thus have been used to design artificial metalloproteins/metalloenzymes during the past few decades. In this review, we focus on the recent progresses in protein design by tuning the noncovalent interactions, including hydrophobic and H-bonding interactions. The topics include redesign and reuse of the heme pocket and other protein scaffolds, design of the heme protein interface, and de novo design of metalloproteins. The informations not only give insights into the metalloenzyme reaction mechanisms but also provide new reactions for future applications.


Notes: ---

Rational Design of Heme Enzymes for Biodegradation of Pollutants Toward a Green Future

Review

Lin, Y.-W.

Biotechnol. Appl. Biochem. 2019, 10.1002/bab.1788

Environmental pollutants, such as industrial dyes and halophenols, are harmful to human health, which urgently demand degradation. Bioremediation has been shown to be a cost‐effective and ecofriendly approach. As reviewed herein, significant progress has been made in the last decade for biodegradation of both industrial dyes and halophenols, by engineering of native dye‐decolorizing peroxidases (DyPs) and dehaloperoxidases (DHPs), and by design of artificial heme enzymes in both native and de novo protein scaffolds. The catalytic efficiency of artificial DyPs and DHPs can be rationally designed comparable to or even beyond those of natural counterparts. The enzymes are on their way from laboratory to industry and will play more crucial roles in environmental protection toward a green future.


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The Third Generation of Artificial Dye-Decolorizing Peroxidase Rationally Designed in Myoglobin

Lin, Y.-W.

ACS Catal. 2019, 9, 7888-7893, 10.1021/acscatal.9b02226

Approaches to degradation of industrial dyes are desirable, of which bioremediation is more favorable. In addition to the use of native enzymes, rational design of artificial enzymes provides an alternative approach. Meanwhile, few designs can achieve a catalytic activity comparable to that of native enzymes. We have previously designed two generations of artificial dye-decolorizing peroxidases (DyPs) in myoglobin (Mb) by introduction of Tyr43 and Trp138 in the heme pocket; however, the activity is moderate. To improve the activity of the artificial DyP, we herein designed a third generation by introduction of an additional Trp (P88W) to the protein surface, named F43Y/F138W/P88W Mb. The third generation of artificial DyP was shown to exhibit a catalytic efficiency exceeding that of various native DyPs and comparable to that of the most efficient native DyPs. Titration of reactive blue 19 (RB19) and molecular docking studies revealed crucial roles of Trp88 in substrate binding and oxidation, which acts as a catalytic site. This study not only provides clues for heme protein design but also suggests that the artificial DyP has potential applications for bioremediation in the future.


Metal: Fe
Ligand type: Porphyrin
Host protein: Myoglobin (Mb)
Anchoring strategy: Dative
Optimization: Genetic
Reaction: Peroxidation
Max TON: 30
ee: ---
PDB: ---
Notes: 3rd generation based on previous studies