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Rhodochelin, a mixed catecholate-hydroxamate type siderophore isolated from Rhodococcus jostii RHA1, holds two L-δ-N-formyl-δ-N-hydroxyornithine (L-fhOrn) moieties essential for proper iron coordination. Previously, bioinformatic and genetic analysis proposed rmo and rft as the genes required for the tailoring of the L-ornithine (L-Orn) precursor [Bosello, M. (2011) J. Am. Chem. Soc.133, 4587-4595]. In order to investigate if both Rmo and Rft constitute a pathway for L-fhOrn biosynthesis, the enzymes were heterologously produced and assayed in vitro. In the presence of molecular oxygen, NADPH and FAD, Rmo monooxygenase was able to convert L-Orn into L-δ-N-hydroxyornithine (L-hOrn). As confirmed in a coupled reaction assay, this hydroxylated intermediate serves as a substrate for the subsequent N(10)-formyl-tetrahydrofolate-dependent (N(10)-fH(4)F) Rtf-catalyzed formylation reaction, establishing a route for the L-fhOrn biosynthesis, prior to its incorporation by the NRPS assembly line. It is of particular interest that a major improvement to this study has been reached with the use of an alternative approach to the chemoenzymatic FolD-dependent N(10)-fH(4)F conversion, also rescuing the previously inactive CchA, the Rft-homologue in coelichelin assembly line [Buchenau, B. (2004) Arch. Microbiol.182, 313-325; Pohlmann, V. (2008) Org. Biomol. Chem.6, 1843-1848]. © 2012 American Chemical Society


Mattia Bosello, Andreas Mielcarek, Tobias W Giessen, Mohamed A Marahiel. An enzymatic pathway for the biosynthesis of the formylhydroxyornithine required for rhodochelin iron coordination. Biochemistry. 2012 Apr 10;51(14):3059-66

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PMID: 22439765

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