Affiliation:
1. Department of Chemistry, University of Zurich, CH-8057 Zurich, Switzerland
Abstract
ABSTRACT
The coenzyme B
12
-dependent isobutyryl coenzyme A (CoA) mutase (ICM) and methylmalonyl-CoA mutase (MCM) catalyze the isomerization of
n
-butyryl-CoA to isobutyryl-CoA and of methylmalonyl-CoA to succinyl-CoA, respectively. The influence that both mutases have on the conversion of
n
- and isobutyryl-CoA to methylmalonyl-CoA and the use of the latter in polyketide biosynthesis have been investigated with the polyether antibiotic (monensin) producer
Streptomyces cinnamonensis
. Mutants prepared by inserting a hygromycin resistance gene (
hygB
) into either
icmA
or
mutB
, encoding the large subunits of ICM and MCM, respectively, have been characterized. The
icmA
::
hygB
mutant was unable to grow on valine or isobutyrate as the sole carbon source but grew normally on butyrate, indicating a key role for ICM in valine and isobutyrate metabolism in minimal medium. The
mutB
::
hygB
mutant was unable to grow on propionate and grew only weakly on butyrate and isobutyrate as sole carbon sources.
13
C-labeling experiments show that in both mutants butyrate and acetoacetate may be incorporated into the propionate units in monensin A without cleavage to acetate units. Hence,
n
-butyryl-CoA may be converted into methylmalonyl-CoA through a carbon skeleton rearrangement for which neither ICM nor MCM alone is essential.
Publisher
American Society for Microbiology
Subject
Molecular Biology,Microbiology
Cited by
46 articles.
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