Neurospora crassa CyPBP37:: A cytosolic stress protein that is able to replace yeast Thi4p function in the synthesis of vitamin B1

Recently, we identified CyPBP37 of Neurospora crassa as a binding partner of cyclophilin4l. CyPBP37 function had not yet been described, although orthologs in other organisms have been implicated in the biosynthesis of the thiazole moiety of thiamine (vitamin B-1) and/or stress-related pathways. Here, CyPBP37 is characterized as an abundant cytosolic protein with a functional NAD-binding site. Saccharomyces cerevisiae mutants lacking Thi4p (the CyPBP37 ortholog) are auxotrophic for vitamin B, (thiamine) but can grow in the presence of the thiazole moiety of thiamine, suggesting a role for Thi4p in the biosynthesis of thiazole. N. crassa CyPBP37 is able to functionally replace Thi4p in yeast thiazole synthesis. Cellular fractionation studies revealed that Thi4p is a cytosolic protein in S. cerevisiae, like its ortholog CyPBP37 in N. crassa. This implies that thiamine synthesis takes place in the cytosol of both organisms and not in the mitochondria, as suggested. The expression of CyPBP37 and Thi4p is repressed by thiamine but not by thiazole in the growth medium. In addition to its function in thiazole synthesis, CyPBP37 is a stress-inducible protein. N. c;,assa cyclophilin41 can chaperone the folding of CyPBP37, its own binding partner. (C) 2004 Elsevier Ltd. All rights reserved.