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J. Biol. Chem., Vol. 277, Issue 25, 22107-22110, June 21, 2002

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ACCELERATED PUBLICATION
Molecular Cloning of CoA Synthase
THE MISSING LINK IN CoA BIOSYNTHESIS^*,

Alexander Zhyvoloup^§, Ivan Nemazanyy^¶, Aleksei Babich, Ganna Panasyuk, Natalya Pobigailo, Mariya Vudmaska, Valeriy Naidenov, Oleksandr Kukharenko, Sergiy Palchevskii, Liliya Savinska, Galina Ovcharenko, Frederique Verdier^§, Taras Valovka^§, Tim Fenton^§, Heike Rebholz^§, Mong-Lien Wang^§, Peter Shepherd, Genadiy Matsuka, Valeriy Filonenko, and Ivan T. Gout^§**

From the  Department of Structure and Function of Nucleic Acid, The Institute of Molecular Biology and Genetics, 150 Zabolotnogo Street, Kyiv 143, Ukraine, the ^§ Ludwig Institute for Cancer Research, 91 Riding House Street, London W1W 7BS, United Kingdom, and the  Department of Biochemistry and Molecular Biology, Royal Free and University College Medical School, Gower Street, London WC1E 6BT, United Kingdom

Coenzyme A functions as a carrier of acetyl and acyl groups in living cells and is essential for numerous biosynthetic, energy-yielding, and degradative metabolic pathways. There are five enzymatic steps in CoA biosynthesis. To date, molecular cloning of enzymes involved in the CoA biosynthetic pathway in mammals has been only reported for pantothenate kinase. In this study, we present cDNA cloning and functional characterization of CoA synthase. It has an open reading frame of 563 aa and encodes a protein of ~60 kDa. Sequence alignments suggested that the protein possesses both phosphopantetheine adenylyltransferase and dephospho-CoA kinase domains. Biochemical assays using wild type recombinant protein confirmed the gene product indeed contained both these enzymatic activities. The presence of intrinsic phosphopantetheine adenylyltransferase activity was further confirmed by site-directed mutagenesis. Therefore, this study describes the first cloning and characterization of a mammalian CoA synthase and confirms this is a bifunctional enzyme containing the last two components of CoA biosynthesis.

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