ISOLATION AND EXPRESSION OF A CDNA-ENCODING THE PRECURSOR FOR A NOVELMEMBER (ACADSB) OF THE ACYL-COA DEHYDROGENASE GENE FAMILY

The acyl-CoA dehydrogenases (ACDs) are a family of mitochondrial enzym es that oxidize straight chain or branched chain acyl-CoAs in the meta bolism of fatty acids or branched chain amino acids. Deficiencies in m embers of this gene family are important causes of human disease. A cD NA encoding the human precursor for a novel member (gene symbol ACADSB ) of the ACD gene family has been isolated and characterized. The open reading frame of 1.3 kb encodes a precursor protein of 431 amino acid s, which is processed in vitro to yield a mature protein of 399 amino acids. The cDNA has significant sequence similarity to other members o f the acyl-CoA dehydrogenase family, with the greatest homology (38%) to the short chain acyl-CoA dehydrogenase. The cDNA was expressed in e ukaryotic (COS) and prokaryotic (Escherichia coil) cells, producing a protein of the expected size, with activity toward the short branched chain acyl-CoA derivatives ((S)-2methylbutyryl-CoA, isobutyryl-CoA, an d 2-methylhexanoyl-CoA), as well as toward the short straight chain ac yl-CoAs (butyryl-CoA and hexanoyl-COA). (C) 1994 Academic Press, Inc.