The yeast pantothenate kinase Cab1 is a master regulator of sterol metabolism and of susceptibility to ergosterol biosynthesis inhibitors

Abstract

are listed on a patent application for targeting pantothenate kinase (PanK) activity for development of antifungal drugs. Choukri Ben Mamoun is the founder of a company that aims to develop such drugs. This article contains Figs. S1 and S2.

Exploring Yeast as a Study Model of Pantothenate Kinase-Associated Neurodegeneration and for the Identification of Therapeutic Compounds

“…As recently demonstrated, the deficit in PANK in yeast leads to different levels of sterol intermediates [ 42 ] and in a yeast model of CoPAN showing a 40% reduction of coenzyme A, the content of intracellular lipid droplets is reduced [ 33 ]. We then evaluated the content of intracellular lipid droplets in the PKAN yeast model.…”

Redesigning therapies for pantothenate kinase–associated neurodegeneration

“…either maintain or only partially reduce enzyme activity. Unlike higher eukaryotes, which express more than one PANK enzyme, fungi encode a single PANK ortholog (22). The S. cerevisiae Pank ortholog, Cab1, is particularly interesting due to its J o u r n a l P r e -p r o o f essential role in cell viability as well as for the presence of mutants that display cell biological defects similar to those seen in PKAN cells.…”

“…In recent years, several animal models of PKAN have been developed, but translation of this knowledge to humans is hampered by physiological and metabolic differences between model organisms and humans ( 11 , 13 , 14 , 15 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ). One key difference is that while all the species used share a homologous pantothenate kinase gene, the number of different orthologs and subcellular localization of the encoded proteins often vary.…”

“…PANK1 is primarily expressed in the liver, kidney, brain, and small intestine but expressed at low levels in other tissues like the liver and skeletal muscle (reads per kilobase of transcript, per million mapped reads <1) ( 29 ). PANK2 , on the other hand, is expressed at moderate levels in most tissues but is highly expressed in the brain, thymus, and prostate ( 22 ). PANK3 is expressed highly in the brain, heart, thymus, and skeletal muscle, with moderate expression levels in other tissues (reads per kilobase of transcript, per million mapped reads >1) ( 22 ).…”

Involvement of Sulfur in the Biosynthesis of Essential Metabolites in Pathogenic Fungi of Animals, Particularly Aspergillus spp.: Molecular and Therapeutic Implications

“…The first step is likely catalyzed by glutamate-cysteine ligase (Gcs1), which catalyzes the condensation of Cys and glutamate to form γ-glutamylcysteine, which is then converted to GSH by the addition of Gly to the C-terminal of γ-glutamylcysteine by glutathione synthase (Gsh2) (Chen et al, 2009). Moreover, both Cys and pantothenic acid are key precursors of the thiol-containing Coenzyme A in yeast, and in other fungi (Chiu et al, 2019). CoA is not only an important co-factor for enzyme-catalyzed reactions, but is the source of 4 -phosphopantetheine for essential post-translational activation of non-ribosomal peptide synthetases and polyketide synthases in fungi (Stack et al, 2009;Sheridan et al, 2015).…”