The 3-ketoacyl-CoA thiolase: an engineered enzyme for carbon chain elongation of chemical compounds
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MINI-REVIEW
The 3-ketoacyl-CoA thiolase: an engineered enzyme for carbon chain elongation of chemical compounds Lixia Liu 1,2 & Shenghu Zhou 1,2 & Yu Deng 1,2 Received: 2 June 2020 / Revised: 9 August 2020 / Accepted: 17 August 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
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. Keywords Claisen condensation . Metabolic engineering . Reverse β-oxidation . Thiolase
Introduction In living systems, the carbon chains of complex compounds are usually formed through iterative Claisen condensation between primers and extender units (Richard and Charles 2002; Zhou et al. 2020a). Generally, the extender units include acetyl-CoA, propionyl-CoA, and glycolyl-CoA, and the primers include acetyl-CoA, propionyl-CoA, glycolyl-CoA, isobutyryl-CoA, succinyl-CoA, and phenylacetyl-CoA Lixia Liu and Shenghu Zhou contributed equally to this work. * Yu Deng [email protected] 1
National Engineering Laboratory for Cereal Fermentation Technology (NELCF), Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu 214122, People’s Republic of China
2
Jiangsu Provincial Research Center for Bioactive Product Processing Technology, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu 214122, People’s Republic of China
(Fig. 1) (Cheong et al. 2016; Zhou et al. 2020a). Zhou et al. reported that thiolases, polyketide synthase, and carboxylases are capable of catalyzing chain extension by using these primers and extender units (Haapalainen et al. 2006; Zhou et al. 2020a). Likewise, Felnagle et al. highlighted the application of isopropylmalate synthase that could condense acetyl-CoAs for chain extension by modular or iterative methods (Felnagle et al. 2012). In these reviews, one of the most extensively studied thiolases called 3-ketoacyl-CoA thiolases (KAT) was not specifica
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