C O M M U N I C A T I O N S
of a mixture of R-hydroxyketone regioisomers (7:8 ) 1.4:1)12 with
ScyC in the presence of both ThDP and Mg2+ resulted in no product
formation (Scheme 2b). The possibility of ScyC inhibition by 7 or
8 was ruled out by doping tandem ScyA/ScyC assay mixtures; no
change in the qualitative rate of formation of ketone 5 was observed
in the presence of 7 and 8 in comparison to a DMSO control. Based
on these experiments, we favor pathway A as a reasonable
mechanism for the action of ScyC.
lation to trap out the annular cyclopentyl[b]indole as an irreversible
event. At the time of our initial experiments we could not readily
explain the preferential formation of a single isomer by ScyA; the
discovery of the ScyC provides that missing insight, as only the
observed ꢀ-ketoacid regioisomer (2) could have a ketone ap-
propriately positioned for cyclization. The ScyC product 5 is only
one oxidation state away from a potential dimerization substrate
(9) that could be progressed to the complete scytonemin skeleton.
We have commented above that direct cyclizations to form
cyclopentyl[b]indole scaffolds have been elusive, indicating that
additional study of the structure and mechanism of ScyC is
warranted. Efforts toward further characterization of this enzyme,
as well as investigation of the remaining steps in scytonemin
biosynthesis, are currently underway.
Scheme 2
Acknowledgment. This work is supported by the NIH
(GM20011). E.P.B. is the recipient of an NIH postdoctoral
fellowship.
Supporting Information Available: Experimental details and
characterization data for new compounds. This material is available
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