Structural studies of RebC, involved in rebeccamycin biosynthesis

BIOL 135

Katherine S. Ryan, ksryan@mit.edu1, Annaleise R. Howard-Jones, annaleise_howard-jones@hms.harvard.edu2, Christopher T. Walsh2, and Catherine L. Drennan, cdrennan@mit.edu3. (1) Department of Biology, MIT, 77 Massachusetts Avenue, Cambridge, MA 02139, (2) Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Ave, Boston, MA 02115, (3) Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Ave, Cambridge, MA 02139
Rebeccamycin, an antitumor compound, is synthesized by L. aerocolonigenes from the precursor L-tryptophan. One step in the biosynthetic pathway involves the net 8-electron oxidation of chlorinated chromopyrrolic acid to generate the rebeccamycin aglycone, which is carried out by the enzymatic pair, RebP and RebC. Biochemical studies show that RebP, when incubated by itself with ferredoxin, flavodoxin NADP+-reductase, and NAD(P)H, is able to create a variety of final products – including the final product, the rebeccamycin aglycone. The presence of RebC, however, greatly accelerates product formation and eliminates all side reactions. To learn more about the function of RebC, its crystal structure was obtained to 1.8Å. The structure of RebC bears much resemblance to phenol hydroxylase, a flavin-dependent monooxygense. This suggests that RebC is also a flavin-dependent monooxygenase, which might react with a yet-unidentified product produced by RebP. We will discuss further findings from the structural and biochemical studies of RebC.
 

Poster Session
8:00 PM-10:00 PM, Monday, August 20, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Biological Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007