Nonribosomal peptide synthesis in Schizosaccharomyces pombe and the architectures of ferrichrome-type siderophore synthetases in fungi.
A nonribosomal peptide synthetase (NRPS) in Schizosaccharomyces pombe, which possesses an unusual structure incorporating three adenylation domains, six thiolation domains and six condensation domains, has been shown to produce the cyclohexapeptide siderophore ferrichrome. One of the adenylation domains is truncated and contains a distorted key motif. Substrate-binding specificities of the remaining two domains were assigned by molecular modelling to glycine and to N-acetyl-N-hydroxy-L-ornithine. Hexapeptide siderophore synthetase genes of Magnaporthe grisea and Fusarium graminearum were both identified and analyzed with respect to substrate-binding sites, and the predicted product ferricrocin was identified in each. A comparative analysis of these synthetase systems, including those of the basidiomycete Ustilago maydis, the homobasidiomycete Omphalotus olearius and the ascomycetes Aspergillus nidulans, Aspergillus fumigatus, Fusarium graminearum, Cochliobolus heterostrophus, Neurospora crassa and Aureobasidium pullulans, revealed divergent domain compositions with respect to their number and positioning, although all produce similar products by iterative processes. A phylogenetic analysis of both NRPSs and associated L-N5-ornithine monooxygenases revealed that ferrichrome-type siderophore biosynthesis has coevolved in fungi with varying in trans interactions of NRPS domains.
Schwecke
Torsten
T
Institute of Chemistry, Technical University Berlin, Franklinstrasse 29, 10587 Berlin, Germany.
Göttling
Kirsten
K
Durek
Pawel
P
Dueñas
Ines
I
Käufer
Norbert F
NF
Zock-Emmenthal
Susanne
S
Staub
Eike
E
Neuhof
Torsten
T
Dieckmann
Ralf
R
von Döhren
Hans
H
D000595:Amino Acid Sequence; D001665:Binding Sites; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D005291:Ferrichrome / Q000737:chemistry / Q000378:metabolism*; D005658:Fungi / Q000201:enzymology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D046908:Peptide Biosynthesis, Nucleic Acid-Independent; D010453:Peptide Synthases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D011487:Protein Conformation; D012568:Schizosaccharomyces / Q000201:enzymology*; D012680:Sensitivity and Specificity; D017262:Siderophores / Q000096:biosynthesis* / Q000737:chemistry; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D017262:Siderophores; D005291:Ferrichrome; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase