Identification of an itaconic acid degrading pathway in itaconic acid producing Aspergillus terreus.
Itaconic acid, one of the most promising and flexible bio-based chemicals, is mainly produced by Aspergillus terreus. Previous studies to improve itaconic acid production in A. terreus through metabolic engineering were mainly focused on its biosynthesis pathway, while the itaconic acid-degrading pathway has largely been ignored. In this study, we used transcriptomic, proteomic, bioinformatic, and in vitro enzymatic analyses to identify three key enzymes, itaconyl-CoA transferase (IctA), itaconyl-CoA hydratase (IchA), and citramalyl-CoA lyase (CclA), that are involved in the catabolic pathway of itaconic acid in A. terreus. In the itaconic acid catabolic pathway in A. terreus, itaconic acid is first converted by IctA into itaconyl-CoA with succinyl-CoA as the CoA donor, and then itaconyl-CoA is hydrated into citramalyl-CoA by IchA. Finally, citramalyl-CoA is cleaved into acetyl-CoA and pyruvate by CclA. Moreover, IctA can also catalyze the reaction between citramalyl-CoA and succinate to generate succinyl-CoA and citramalate. These results, for the first time, identify the three key enzymes, IctA, IchA, and CclA, involved in the itaconic acid degrading pathway in itaconic acid producing A. terreus. The results will facilitate the improvement of itaconic acid production by metabolically engineering the catabolic pathway of itaconic acid in A. terreus.
Key Laboratory of Biofuels, Shandong Provincial Key Laboratory of Synthetic Biology, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, 266101, China.
Mei
M
Chen
Key Laboratory of Biofuels, Shandong Provincial Key Laboratory of Synthetic Biology, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, 266101, China.|University of Chinese Academy of Sciences, Beijing, 100049, China.
Xuenian
X
Huang
Key Laboratory of Biofuels, Shandong Provincial Key Laboratory of Synthetic Biology, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, 266101, China.|University of Chinese Academy of Sciences, Beijing, 100049, China.
Chengwei
C
Zhong
Key Laboratory of Biofuels, Shandong Provincial Key Laboratory of Synthetic Biology, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, 266101, China.|National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, China.
Jianjun
J
Li
Key Laboratory of Biofuels, Shandong Provincial Key Laboratory of Synthetic Biology, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, 266101, China. lvxf@qibebt.ac.cn.
Xuefeng
X
Lu
D001230:Aspergillus / Q000378:metabolism*; D053898:Biosynthetic Pathways / Q000502:physiology*; D019755:Carbon-Carbon Lyases / Q000378:metabolism*; D015256:Coenzyme A-Transferases / Q000378:metabolism*; D005656:Fungal Proteins / Q000378:metabolism*; D006836:Hydro-Lyases / Q000378:metabolism*; D060847:Metabolic Engineering; D040901:Proteomics; D013386:Succinates / Q000378:metabolism*
D005656:Fungal Proteins; D013386:Succinates; D015256:Coenzyme A-Transferases; D019755:Carbon-Carbon Lyases; D006836:Hydro-Lyases; C005229:itaconic acid
Aspergillus terreus; Degradation pathway; Itaconic acid; Metabolic engineering