title: ATP-citrate lyase is required for production of cytosolic acetyl coenzyme A and development in Aspergillus nidulans.
abstract: Acetyl coenzyme A (CoA) is a central metabolite in carbon and energy metabolism and in the biosynthesis of cellular molecules. A source of cytoplasmic acetyl-CoA is essential for the production of fatty acids and sterols and for protein acetylation, including histone acetylation in the nucleus. In Saccharomyces cerevisiae and Candida albicans acetyl-CoA is produced from acetate by cytoplasmic acetyl-CoA synthetase, while in plants and animals acetyl-CoA is derived from citrate via ATP-citrate lyase. In the filamentous ascomycete Aspergillus nidulans, tandem divergently transcribed genes (aclA and aclB) encode the subunits of ATP-citrate lyase, and we have deleted these genes. Growth is greatly diminished on carbon sources that do not result in cytoplasmic acetyl-CoA, such as glucose and proline, while growth is not affected on carbon sources that result in the production of cytoplasmic acetyl-CoA, such as acetate and ethanol. Addition of acetate restores growth on glucose or proline, and this is dependent on facA, which encodes cytoplasmic acetyl-CoA synthetase, but not on the regulatory gene facB. Transcription of aclA and aclB is repressed by growth on acetate or ethanol. Loss of ATP-citrate lyase results in severe developmental effects, with the production of asexual spores (conidia) being greatly reduced and a complete absence of sexual development. This is in contrast to Sordaria macrospora, in which fruiting body formation is initiated but maturation is defective in an ATP-citrate lyase mutant. Addition of acetate does not repair these defects, indicating a specific requirement for high levels of cytoplasmic acetyl-CoA during differentiation. Complementation in heterokaryons between aclA and aclB deletions for all phenotypes indicates that the tandem gene arrangement is not essential.
authors.affiliation: Department of Genetics, University of Melbourne, Parkville, Victoria 3010, Australia. mjhynes@unimelb.edu.au
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hynes
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Murray
mesh_terms: D001275:ATP Citrate (pro-S)-Lyase / Q000235:genetics / Q000378:metabolism*; D000085:Acetates / Q000494:pharmacology; D000105:Acetyl Coenzyme A / Q000096:biosynthesis*; D001233:Aspergillus nidulans / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development*; D002244:Carbon / Q000494:pharmacology; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology*; D005463:Fluoroacetates / Q000494:pharmacology; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D005800:Genes, Fungal / Q000235:genetics; D005816:Genetic Complementation Test; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D046468:Sexual Development / Q000187:drug effects; D013172:Spores, Fungal / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development
chemical_list: D000085:Acetates; D005463:Fluoroacetates; D005656:Fungal Proteins; D000105:Acetyl Coenzyme A; D002244:Carbon; D001275:ATP Citrate (pro-S)-Lyase