DEVELOPMENTAL REGULATION OF THE GENE FOR FORMATE DEHYDROGENASE IN NEUROSPORA-CRASSA

We have isolated and characterized a gene,fdh, from Neurospora crassa which is developmentally regulated and which produces formate dehydrog enase activity when expressed in Escherichia coli. The gene is closely linked (less than 0.6 kb apart) to the ku-5 gene encoding mitochondri al leucyl-tRNA synthetase; the two genes are transcribed convergently from opposite strands. The expression patterns of these genes differ:f dh mRNA is found only during conidiation and early germination and is not detectable during mycelial growth, while ku-5 mRNA appears during germination and mycelial growth. The structure of the fdh gene was det ermined from the sequence of cDNA and genomic DNA clones and from mRNA mapping studies. The gene encodes a 375-amino-acid-long protein with sequence similarity to NAD-dependent dehydrogenases of the E. coli 3-p hosphoglycerate dehydrogenase (serA gene product) subfamily. In partic ular, there is striking sequence similarity (52% identity) to formate dehydrogenase from Pseudomonas sp. strain 101. All of the residues tho ught to interact with NAD in the crystal structure of the Pseudomonas enzyme are conserved in the N. crassa enzyme. We have further shown th at expression of the N. crassa gene in E. coli leads to the production of formate dehydrogenase activity, indicating that the N. crassa gene specifies a functional polypeptide.