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Published online on July 7, 2005, 10.1073/pnas.0504412102
PNAS | July 19, 2005 | vol. 102 | no. 29 | 10111-10116


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From The Cover
BIOCHEMISTRY
SyrB2 in syringomycin E biosynthesis is a nonheme FeII {alpha}-ketoglutarate- and O2-dependent halogenase

Frédéric H. Vaillancourt, Jun Yin, and Christopher T. Walsh *

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115

Contributed by Christopher T. Walsh, May 27, 2005

The nine-residue lipodepsipeptide syringomycin E, elaborated as a phytotoxin by Pseudomonas syringae pv. syringae B301D contains a 4-Cl-L-Thr-9 moiety where failure to chlorinate results in a 3-fold drop in biological activity. The proteins SyrB1 and SyrB2 encoded by the biosynthetic cluster are shown to act as a substrate and enzyme pair for SyrB2-mediated chlorination of the aminoacyl-S-enzyme L-Thr-S-SyrB1. SyrB2 is a member of the nonheme FeII {alpha}-ketoglutarate-dependent enzyme superfamily, and requires O2 and {alpha}-ketoglutarate as well as chloride ion to carry out monochlorination of the -CH3 group of L-Thr-S-SyrB1. Chlorination of L-Thr-S-SyrB1 was validated by thioesterase-mediated release of L-Thr and 4-Cl-L-Thr, N-derivatization as fluorescent isoindoles, and HPLC separation compared with authentic standards. Incubations with L-[14C]Thr and [36Cl-] as well as MS of the released products further validated identification. Enzymatic oxidative halogenation is a previously uncharacterized reaction type for nonheme FeII enzymes and may be the general mode for biosynthetic halogenation of aliphatic carbons of natural products.

natural product biosynthesis | enzymology | organohalogen

Abbreviation: {alpha}-KG, {alpha}-ketoglutarate.

* To whom correspondence should be addressed. E-mail: christopher_walsh{at}hms.harvard.edu.

© 2005 by The National Academy of Sciences of the USA


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