Publications by authors named "Kevin J Sheridan"

The Photosystem II water-plastoquinone oxidoreductase is a multi-subunit complex which catalyses the light-driven oxidation of water to molecular oxygen in oxygenic photosynthesis. The D1 reaction centre protein exists in multiple forms in cyanobacteria, including D1 which is expressed under far-red light. We investigated the role of Phe184 that is found in the lumenal cd-loop of D1 but is typically an isoleucine in other D1 isoforms.

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The wavelengths of light harvested in oxygenic photosynthesis are ~400-700 nm. Some cyanobacteria respond to far-red light exposure via a process called far-red light photoacclimation which enables absorption of light at wavelengths >700 nm and its use to support photosynthesis. Far-red-light-induced changes include up-regulation of alternative copies of multiple proteins of Photosystem II (PS II).

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The psbA gene family in cyanobacteria encodes different forms of the D1 protein that is part of the Photosystem II reaction centre. We have identified a phylogenetically distinct D1 group that is intermediate between previously identified G3-D1 and G4-D1 proteins (Cardona et al. Mol Biol Evol 32:1310-1328, 2015).

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Fungal sulfur uptake is required for incorporation into the sidechains of the amino acids cysteine and methionine, and is also essential for the biosynthesis of the antioxidant glutathione (GSH), -adenosylmethionine (SAM), the key source of methyl groups in cellular transmethylation reactions, and -adenosylhomocysteine (SAH). Biosynthesis of redox-active gliotoxin in the opportunistic fungal pathogen has been elucidated over the past 10 years. Some fungi which produce gliotoxin-like molecular species have undergone unexpected molecular rewiring to accommodate this high-risk biosynthetic process.

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Ergothioneine (EGT; 2-mercaptohistidine trimethylbetaine) is a trimethylated and sulphurised histidine derivative which exhibits antioxidant properties. Here we report that deletion of Aspergillus fumigatus egtA (AFUA_2G15650), which encodes a trimodular enzyme, abrogated EGT biosynthesis in this opportunistic pathogen. EGT biosynthetic deficiency in A.

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Mechanistic studies on gliotoxin biosynthesis and self-protection in Aspergillus fumigatus, both of which require the gliotoxin oxidoreductase GliT, have revealed a rich landscape of highly novel biochemistries, yet key aspects of this complex molecular architecture remain obscure. Here we show that an A. fumigatus ΔgliA strain is completely deficient in gliotoxin secretion but still retains the ability to efflux bisdethiobis(methylthio)gliotoxin (BmGT).

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Non-ribosomal peptide (NRP) synthesis in fungi requires a ready supply of proteogenic and non-proteogenic amino acids which are subsequently incorporated into the nascent NRP via a thiotemplate mechanism catalyzed by NRP synthetases. Substrate amino acids can be modified prior to or during incorporation into the NRP, or following incorporation into an early stage amino acid-containing biosynthetic intermediate. These post-incorporation modifications involve a range of additional enzymatic activities including but not exclusively, monooxygenases, methyltransferases, epimerases, oxidoreductases, and glutathione S-transferases which are essential to effect biosynthesis of the final NRP.

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A combined proteomics and metabolomics approach was utilised to advance the identification and characterisation of secondary metabolites in Aspergillus fumigatus. Here, implementation of a shotgun proteomic strategy led to the identification of non-redundant mycelial proteins (n = 414) from A. fumigatus including proteins typically under-represented in 2-D proteome maps: proteins with multiple transmembrane regions, hydrophobic proteins and proteins with extremes of molecular mass and pI.

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Life expectancy for the 400 000 adults with cerebral palsy (CP) in the USA is increasing. Although there is a perception of increased fractured rate in the adult with CP, it has not been well studied. Low bone mineral density is found in more than 50% of adults with a variety of disabilities, including CP.

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