The Methylcitrate Cycle and Its Crosstalk with the Glyoxylate Cycle and Tricarboxylic Acid Cycle in Pathogenic Fungi
Zhicheng Huang,
Qing Wang,
Irshad Ali Khan,
Yan Li,
Jing Wang,
Jiaoyu Wang,
Xiaohong Liu,
Fucheng Lin,
Jianping Lu
Affiliations
Zhicheng Huang
State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, College of Life Sciences, Zhejiang University, Hangzhou 310058, China
Qing Wang
State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, College of Life Sciences, Zhejiang University, Hangzhou 310058, China
Irshad Ali Khan
Department of Agriculture, The University of Swabi, Khyber 29380, Pakistan
Yan Li
State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, College of Life Sciences, Zhejiang University, Hangzhou 310058, China
Jing Wang
State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China
Jiaoyu Wang
State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China
Xiaohong Liu
Institute of Biotechnology, Zhejiang University, Hangzhou 310058, China
Fucheng Lin
State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China
Jianping Lu
State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, College of Life Sciences, Zhejiang University, Hangzhou 310058, China
In fungi, the methylcitrate cycle converts cytotoxic propionyl-coenzyme A (CoA) to pyruvate, which enters gluconeogenesis. The glyoxylate cycle converts acetyl-CoA to succinate, which enters gluconeogenesis. The tricarboxylic acid cycle is a central carbon metabolic pathway that connects the methylcitrate cycle, the glyoxylate cycle, and other metabolisms for lipids, carbohydrates, and amino acids. Fungal citrate synthase and 2-methylcitrate synthase as well as isocitrate lyase and 2-methylisocitrate lyase, each evolved from a common ancestral protein. Impairment of the methylcitrate cycle leads to the accumulation of toxic intermediates such as propionyl-CoA, 2-methylcitrate, and 2-methylisocitrate in fungal cells, which in turn inhibits the activity of many enzymes such as dehydrogenases and remodels cellular carbon metabolic processes. The methylcitrate cycle and the glyoxylate cycle synergistically regulate carbon source utilization as well as fungal growth, development, and pathogenic process in pathogenic fungi.
