MOLECULAR-CLONING SEQUENCING AND SEQUENCE-ANALYSIS OF THE FOX-2 GENE OF NEUROSPORA-CRASSA ENCODING THE MULTIFUNCTIONAL BETA-OXIDATION PROTEIN

We present the molecular cloning and sequencing of genomic and cDNA cl ones of the fox-2 gene of Neurospora crassa, encoding the multifunctio nal beta-oxidation protein (MFP). The coding region of the fox-2 gene is interrupted by three introns, one of which appears to be inefficien tly spliced out. The encoded protein comprises 894 amino acid residues and exhibits 45% and 47% sequence identity with the MFPs of Candida t ropicalis and Saccharomyces cerevisiae, respectively. Sequence analysi s identifies three regions of the fungal MFPs that are highly conserve d. These regions are separated by two segments that resemble linkers b etween domains of other MFPs, suggesting a three-domain structure. The first and second conserved regions of each MFP are homologous to each other and to members of the short-chain alcohol dehydrogenase family. We discuss these homologies in view of recent findings that fungal MF Ps contain enoyl-CoA hydratase 2 and D-3-hydroxyacyl-CoA dehydrogenase activities, converting trans-2-enoyl-CoA via D-3-hydroxyacyl-CoA to 3 -ketoacyl-CoA. In contrast to its counterparts in yeasts, the Neurospo ra MFP does not have a C-terminal sequence resembling the SKL motif in volved in protein targeting to microbodies.