LanV, a bifunctional enzyme: aromatase and ketoreductase during landomycin A biosynthesis.
LanV is involved in the biosynthesis of landomycin A. The exact function of this enzyme was elucidated with combinatorial biosynthesis by using Streptomyces fradiae mutants that produce urdamycin A. After expression of lanV in S. fradiae DeltaurdM, which is a mutant that accumulates rabelomycin, urdamycinon B and urdamycin B were found to be produced by the strain. This result indicates that LanV is involved in the 6-ketoreduction of the angucycline core, which preceeds a 5,6-dehydration reaction. 9-C-D-Olivosyltetrangulol was also produced by this strain; this demonstrates that LanV catalyses the aromatization of ring A of the angucycline structure. Coexpression of lanV and lanGT2 in S. fradiae AO, a mutant that lacks all four urdamycin glycosyltransferases, resulted in the production of tetrangulol and the glycoside landomycin H, both of which have an aromatic ring A. As glycosylated angucyclines were not observed after expression of lanGT2 in the absence of lanV, we conclude that LanGT2 needs an aromatized ring A for substrate recognition.
Mayer
Almuth
A
Albert-Ludwigs-Universität, Institut für Pharmazeutische Wissenschaften, Stefan-Meier-Strasse 19, 79104 Freiburg, Germany.
Taguchi
Takaaki
T
Linnenbrink
Anton
A
Hofmann
Carsten
C
Luzhetskyy
Andriy
A
Bechthold
Andreas
A
D000617:Aminoglycosides / Q000096:biosynthesis*; D000970:Antineoplastic Agents; D001141:Aromatase / Q000378:metabolism*; D016695:Glycosyltransferases / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism*; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics
D000617:Aminoglycosides; D000970:Antineoplastic Agents; C064648:landomycin A; D010088:Oxidoreductases; D001141:Aromatase; D016695:Glycosyltransferases; C514966:LanV enzyme, Streptomyces