Role of the cytochrome P450 NocL in nocardicin A biosynthesis.
The nocardicins are members of a class of monocyclic beta-lactam antibiotics produced by the actinomycete Nocardia uniformis subsp. tsuyamanesis (ATCC 21806). The oxime moiety in nocardicin A is required for full biological activity and is rare among natural products. A putative gene cluster encoding the enzymes of the nocardicin biosynthetic pathway has been identified. Among these, NocL shows similarity to cytochromes P450. We describe its heterologous expression and demonstrate its role in the formation of this unusual structural feature in nocardicin A. This is the first gene from this pathway to be expressed and its function established, and it is the first example of oxime formation from a primary amine in bacteria unambiguously linked to a cytochrome P450.
Kelly
Wendy L
WL
Department of Chemistry, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
Townsend
Craig A
CA
D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D002384:Catalysis; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D007769:Lactams; D009615:Nocardia / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D010091:Oximes / Q000378:metabolism
D000900:Anti-Bacterial Agents; D007769:Lactams; D010091:Oximes; C027318:nocardicin; D003577:Cytochrome P-450 Enzyme System