Send to

Choose Destination
J Am Chem Soc. 2008 Jun 18;130(24):7554-5. doi: 10.1021/ja8025278. Epub 2008 May 23.

Myxochelin biosynthesis: direct evidence for two- and four-electron reduction of a carrier protein-bound thioester.

Author information

Pharmaceutical Biotechnology, Saarland University, P.O. Box 151150, 66041 Saarbrücken, Germany.


Microorganisms produce small molecules known as siderophores to scavenge iron from the environment. Insight into iron acquisition in myxobacteria has been provided recently by the sequencing of the gene cluster for the catecholate myxochelins A and B, from the myxobacterium Stigmatella aurantiaca Sg a15. The gene cluster contains enzymes (MxcCDEF) for assembly of 2,3-dihydroxybenzoic acid (DHBA), an amino transferase, MxcL, and a nonribosomal peptide synthetase (NRPS) subunit, MxcG. In the proposed pathway to the myxochelins, two molecules of DHBA are condensed with the two amino groups of lysine, which is itself tethered to the peptidyl carrier protein domain (PCP) of MxcG. The resulting thioester is then reduced by the NADPH-dependent reductase (Red) domain of MxcG to generate an aldehyde intermediate; subsequent Red-catalyzed reduction yields myxochelin A, while transamination by MxcL produces myxochelin B. Although myxochelin A has been obtained successfully in vitro, it has not been possible to date to reconstitute the transamination reaction to give myxochelin B nor to unequivocally establish the intermediacy of the aldehyde. We report here the successful biosynthesis of myxochelin B in vitro. Furthermore, we demonstrate for the first time the existence of an aldehyde intermediate in the four-electron reduction of a PCP-bound thioester. Finally, we show that the relative levels of myxochelin A and B are likely to be controlled by the direct competition of MxcL and the MxcG Red domain for a free aldehyde intermediate.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for American Chemical Society
Loading ...
Support Center