Discovery, Design, and Structural Characterization of Alkane-Producing Enzymes across the Ferritin-like Superfamily
To complement established rational and evolutionary protein design approaches, significant efforts are being made to utilize computational modeling and the diversity of naturally occurring protein sequences. Here, we combine structural biology, genomic mining, and computational modeling to identify structural features critical to aldehyde deformylating oxygenases (ADOs), an enzyme family that has significant implications in synthetic biology and chemoenzymatic synthesis. Through these efforts, we discovered latent ADO-like function across the ferritin-like superfamily in various species of Bacteria and Archaea. We created a machine learning model that uses protein structural features to discriminate ADO-like activity. Computational enzyme design tools were then utilized to introduce ADO-like activity into the small subunit of Escherichia coli class I ribonucleotide reductase. The integrated approach of genomic mining, structural biology, molecular modeling, and machine learning has the potential to be utilized for rapid discovery and modulation of functions across enzyme families.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:59 |
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| Enthalten in: |
Biochemistry - 59(2020), 40 vom: 13. Okt., Seite 3834-3843 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mak, Wai Shun [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 22.03.2021 Date Revised 22.03.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1021/acs.biochem.0c00665 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM315078502 |
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| 500 | |a Date Revised 22.03.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a To complement established rational and evolutionary protein design approaches, significant efforts are being made to utilize computational modeling and the diversity of naturally occurring protein sequences. Here, we combine structural biology, genomic mining, and computational modeling to identify structural features critical to aldehyde deformylating oxygenases (ADOs), an enzyme family that has significant implications in synthetic biology and chemoenzymatic synthesis. Through these efforts, we discovered latent ADO-like function across the ferritin-like superfamily in various species of Bacteria and Archaea. We created a machine learning model that uses protein structural features to discriminate ADO-like activity. Computational enzyme design tools were then utilized to introduce ADO-like activity into the small subunit of Escherichia coli class I ribonucleotide reductase. The integrated approach of genomic mining, structural biology, molecular modeling, and machine learning has the potential to be utilized for rapid discovery and modulation of functions across enzyme families | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 7 | |a Aldehydes |2 NLM | |
| 650 | 7 | |a Alkanes |2 NLM | |
| 650 | 7 | |a Bacterial Proteins |2 NLM | |
| 650 | 7 | |a Ferritins |2 NLM | |
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| 650 | 7 | |a Oxygenases |2 NLM | |
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| 650 | 7 | |a Ribonucleotide Reductases |2 NLM | |
| 650 | 7 | |a EC 1.17.4.- |2 NLM | |
| 700 | 1 | |a Wang, XiaoKang |e verfasserin |4 aut | |
| 700 | 1 | |a Arenas, Rigoberto |e verfasserin |4 aut | |
| 700 | 1 | |a Cui, Youtian |e verfasserin |4 aut | |
| 700 | 1 | |a Bertolani, Steve |e verfasserin |4 aut | |
| 700 | 1 | |a Deng, Wen Qiao |e verfasserin |4 aut | |
| 700 | 1 | |a Tagkopoulos, Ilias |e verfasserin |4 aut | |
| 700 | 1 | |a Wilson, David K |e verfasserin |4 aut | |
| 700 | 1 | |a Siegel, Justin B |e verfasserin |4 aut | |
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