University of Oulu

Harijan, R. K., Dalwani, S., Kiema, T.-R., Venkatesan, R., & Wierenga, R. K. (2023). Thiolase: A versatile biocatalyst employing coenzyme a–thioester chemistry for making and breaking c–c bonds. Annual Review of Biochemistry, 92(1), 351–384.

Thiolase : a versatile biocatalyst employing coenzyme A–thioester chemistry for making and breaking C–C bonds

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Author: Harijan, Rajesh K.1; Dalwani, Subhadra2; Kiema, Tiila-Riikka2,3;
Organizations: 1Department of Biochemistry, Albert Einstein College of Medicine, New York, NY, USA
2Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
3Biocenter Oulu, University of Oulu, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 3.6 MB)
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Language: English
Published: Annual Reviews, 2023
Publish Date: 2023-11-03


Thiolases are CoA-dependent enzymes that catalyze the thiolytic cleavage of 3-ketoacyl-CoA, as well as its reverse reaction, which is the thioester-dependent Claisen condensation reaction. Thiolases are dimers or tetramers (dimers of dimers). All thiolases have two reactive cysteines: (a) a nucleophilic cysteine, which forms a covalent intermediate, and (b) an acid/base cysteine. The best characterized thiolase is the Zoogloea ramigera thiolase, which is a bacterial biosynthetic thiolase belonging to the CT-thiolase subfamily. The thiolase active site is also characterized by two oxyanion holes, two active site waters, and four catalytic loops with characteristic amino acid sequence fingerprints. Three thiolase subfamilies can be identified, each characterized by a unique sequence fingerprint for one of their catalytic loops, which causes unique active site properties. Recent insights concerning the thiolase reaction mechanism, as obtained from recent structural studies, as well as from classical and recent enzymological studies, are addressed, and open questions are discussed.

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Series: Annual review of biochemistry
ISSN: 0066-4154
ISSN-E: 1545-4509
ISSN-L: 0066-4154
Volume: 92
Pages: 351 - 384
DOI: 10.1146/annurev-biochem-052521-033746
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
Copyright information: © 2023 by the author(s). This work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See credit lines of images or other third-party material in this article for license information.