Affiliation:
1. Department of Infectious Diseases, Novartis Institutes for BioMedical Research, 500 Technology Square, Cambridge, Massachusetts 02139
Abstract
ABSTRACT
Coenzyme A (CoA) plays a central and essential role in all living organisms. The pathway leading to CoA biosynthesis has been considered an attractive target for developing new antimicrobial agents with novel mechanisms of action. By using an arabinose-regulated expression system, the essentiality of
coaBC
, a single gene encoding a bifunctional protein catalyzing two consecutive steps in the CoA pathway converting 4′-phosphopantothenate to 4′-phosphopantetheine, was confirmed in
Escherichia coli
. Utilizing this regulated
coaBC
strain, it was further demonstrated that
E. coli
can effectively metabolize pantethine to bypass the requirement for
coaBC
. Interestingly, pantethine cannot be used by
Pseudomonas aeruginosa
to obviate
coaBC
. Through reciprocal complementation studies in combination with biochemical characterization, it was demonstrated that the differential characteristics of pantethine utilization in these two microorganisms are due to the different substrate specificities associated with endogenous pantothenate kinase, the first enzyme in the CoA biosynthetic pathway encoded by
coaA
in
E. coli
and
coaX
in
P. aeruginosa
.
Publisher
American Society for Microbiology
Subject
Molecular Biology,Microbiology
Cited by
41 articles.
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