title: Functional and phylogenetic divergence of fungal adenylate-forming reductases.
abstract: A key step in fungal L-lysine biosynthesis is catalyzed by adenylate-forming L-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 functional in vitro characterization of four reductases which were heterologously produced in Escherichia coli. The Ceriporiopsis 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 by Ceriporiopsis subvermispora Nps3 as the first biochemically characterized L-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.
authors.affiliation: Friedrich-Schiller-Universität Jena, Department Pharmaceutical Microbiology at the Hans-Knöll-Institute, Jena, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kalb
authors.affiliation: Friedrich-Schiller-Universität Jena, Department Pharmaceutical Microbiology at the Hans-Knöll-Institute, Jena, Germany.
authors.forename: Gerald
authors.initials: G
authors.lastname: Lackner
authors.affiliation: Friedrich-Schiller-Universität Jena, Department Pharmaceutical Microbiology at the Hans-Knöll-Institute, Jena, Germany dirk.hoffmeister@hki-jena.de.
authors.forename: Dirk
authors.initials: D
authors.lastname: Hoffmeister
mesh_terms: D001231:Aspergillus flavus / Q000201:enzymology / Q000235:genetics; D055453:Coriolaceae / Q000201:enzymology* / Q000235:genetics; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics; D064429:Fatty Acid Synthases / Q000235:genetics / Q000378:metabolism; D005287:Ferredoxin-NADP Reductase / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D050647:L-Aminoadipate-Semialdehyde Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D008239:Lysine / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics / Q000378:metabolism; D010802:Phylogeny; D000072417:Protein Domains; D014443:Tyrosine / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; D014443:Tyrosine; D005287:Ferredoxin-NADP Reductase; D050647:L-Aminoadipate-Semialdehyde Dehydrogenase; C036543:short chain trans-2-enoyl-CoA reductase; D009247:NADH, NADPH Oxidoreductases; D064429:Fatty Acid Synthases; D008239:Lysine
references.citation: Cell Mol Life Sci. 2008 Dec;65(24):3895-906
references.pmid: 19011750
references.citation: Nat Prod Rep. 2007 Apr;24(2):393-416
references.pmid: 17390002
references.citation: Mol Genet Genomics. 2003 May;269(2):271-9
references.pmid: 12756539
references.citation: Mol Gen Genet. 1998 Sep;259(5):549-56
references.pmid: 9790587
references.citation: Fungal Genet Biol. 2008 Nov;45(11):1487-96
references.pmid: 18805498
references.citation: Trends Biotechnol. 2009 Mar;27(3):151-7
references.pmid: 19195728
references.citation: Biochemistry. 1999 May 11;38(19):6171-7
references.pmid: 10320345
references.citation: Crit Rev Microbiol. 1985;12(2):131-51
references.pmid: 3928261
references.citation: Appl Microbiol Biotechnol. 2012 Nov;96(3):739-48
references.pmid: 22627757
references.citation: Eur J Biochem. 2003 May;270(9):1900-15
references.pmid: 12709048
references.citation: J Biol Chem. 2003 Mar 7;278(10):8250-6
references.pmid: 12509419
references.citation: Proc Natl Acad Sci U S A. 2013 Oct 15;110(42):17065-70
references.pmid: 24082142
references.citation: Nucleic Acids Res. 2002 Jul 15;30(14):3059-66
references.pmid: 12136088
references.citation: Proc Natl Acad Sci U S A. 2012 Apr 3;109(14):5458-63
references.pmid: 22434909
references.citation: Nat Prod Rep. 2003 Jun;20(3):275-87
references.pmid: 12828367
references.citation: Anal Biochem. 1976 May 7;72:248-54
references.pmid: 942051
references.citation: Science. 2012 Jun 29;336(6089):1715-9
references.pmid: 22745431
references.citation: BMC Evol Biol. 2003 May 8;3:9
references.pmid: 12735797
references.citation: Chem Biol. 1999 Aug;6(8):493-505
references.pmid: 10421756
references.citation: J Bacteriol. 2001 Dec;183(24):7120-5
references.pmid: 11717270
references.citation: Chem Biol. 2014 Feb 20;21(2):257-63
references.pmid: 24412543
references.citation: BMC Evol Biol. 2002 Apr 03;2:6
references.pmid: 11931673
references.citation: Syst Biol. 2012 May;61(3):539-42
references.pmid: 22357727
references.citation: Science. 2011 Aug 5;333(6043):762-5
references.pmid: 21764756
references.citation: Chem Biol. 2007 Jun;14(6):635-44
references.pmid: 17584611
references.citation: Mol Gen Genet. 1983;191(1):66-73
references.pmid: 6350829
references.citation: Chem Biol. 2001 Jul;8(7):725-38
references.pmid: 11451672
references.citation: Mol Gen Genet. 2001 Feb;264(6):755-62
references.pmid: 11254122
references.citation: Angew Chem Int Ed Engl. 2013 Jan 28;52(5):1590-4
references.pmid: 23281040
references.citation: J Mol Biol. 1990 Oct 5;215(3):403-10
references.pmid: 2231712