Functional and Phylogenetic Divergence of Fungal Adenylate-Forming Reductases

A key step in fungall -lysine biosynthesis is catalyzed by adenylate-formingl -α-aminoadipic acid reductases, organized in domains for adenylation, thiolation, and the reduction step. However, the genomes of numerous ascomycetes and basidiomycetes contain an unexpectedly large number of additional genes encoding similar but functionally distinct enzymes. Here, we describe the functionalin vitro characterization of four reductases which were heterologously produced inEscherichia coli . TheCeriporiopsis subvermispora serine reductase Nps1 features a terminal ferredoxin-NADP+ reductase (FNR) domain and thus belongs to a hitherto undescribed class of fungal multidomain enzymes. The second major class is characterized by the canonical terminal short-chain dehydrogenase/reductase domain and represented byCeriporiopsis subvermispora Nps3 as the first biochemically characterizedl -α-aminoadipic acid reductase of basidiomycete origin.Aspergillus flavus l -tyrosine reductases LnaA and LnbA are members of a distinct phylogenetic clade. Phylogenetic analysis supports the view that fungal adenylate-forming reductases are more diverse than previously recognized and belong to four distinct classes.