Abstract
Because of their function of catalyzing the rearrangement of the carbon chains, thiolases have attracted increasing attentions over the past decades. The 3-ketoacyl-CoA thiolase (KAT) is a member of the thiolase, which is capable of catalyzing the Claisen condensation reaction between the two acyl-CoAs, thereby achieving carbon chain elongation. In this way, diverse value-added compounds might be synthesized starting from simple small CoA thioesters. However, most KATs are hampered by low stability and poor substrate specificity, which has hindered the development of large-scale biosynthesis. In this review, the common characteristics in the three-dimensional structure of KATs from different sources are summarized. Moreover, structure-guided rational engineering is discussed as a strategy for enhancing the performance of KATs. Finally, we reviewed the metabolic engineering applications of KATs for producing various energy-storage molecules, such as n-butanol, fatty acids, dicarboxylic acids, and polyhydroxyalkanoates.
Key points
• Summarize the structural characteristics and catalyzation mechanisms of KATs.
• Review on the rational engineering to enhance the performance of KATs.
• Discuss the applications of KATs for producing energy-storage molecules.
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Acknowledgments
This work was supported by the National Key R&D Program of China (2019YFA0905502), the National Natural Science Foundation of China (21877053, 31900066), the Top-Notch Academic Programs Project of Jiangsu Higher Education Institutions (TAPP), the National First-class Discipline Program of Light Industry Technology and Engineering (LITE2018-24), and the Fundamental Research Funds for the Central Universities (JUSRP12056, JUSRP51705A).
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Y. D. and S. Z. designed the structure of this review. Y. D. and S. Z. revised the manuscript. L.L. wrote the manuscript. All the authors read and approved the final manuscript.
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Liu, L., Zhou, S. & Deng, Y. The 3-ketoacyl-CoA thiolase: an engineered enzyme for carbon chain elongation of chemical compounds. Appl Microbiol Biotechnol 104, 8117–8129 (2020). https://doi.org/10.1007/s00253-020-10848-w
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DOI: https://doi.org/10.1007/s00253-020-10848-w