| IUPAC Name | [(6E,8E,10E,16Z)-15-hydroxy-5-methoxy-14,16-dimethyl-3,22,24-trioxo-2-azabicyclo[18.3.1]tetracosa-1(23),6,8,10,16,20-hexaen-13-yl] (2R)-2-(cyclohexanecarbonylamino)propanoate |
| InChI | InChI=1S/C36H48N2O8/c1-23-14-13-17-27-20-28(39)21-30(34(27)42)38-32(40)22-29(45-4)18-11-6-5-7-12-19-31(24(2)33(23)41)46-36(44)25(3)37-35(43)26-15-9-8-10-16-26/h5-7,11-12,14,18,20-21,24-26,29,31,33,41H,8-10,13,15-17,19,22H2,1-4H3,(H,37,43)(H,38,40)/b6-5+,12-7+,18-11+,23-14-/t24?,25-,29?,31?,33?/m1/s1 |
| Reference | 1. Biochemistry. 2000 Jun 27;39(25):7595-604.
<br><br>
A novel delta(3),delta(2)-enoyl-CoA isomerase involved in the biosynthesis of the
cyclohexanecarboxylic acid-derived moiety of the polyketide ansatrienin A.
<br>
Patton SM(1), Cropp TA, Reynolds KA.
<br>
Author information: <br>
(1)Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond
23219, USA.
<br><br>
The side chain of the antifungal polyketide ansatrienin A produced by
Streptomyces collinus contains a cyclohexanecarboxylic acid (CHC) derived moiety.
This CHC in the coenzyme A activated form (CHC-CoA) is derived from shikimic acid
via a pathway in which the penultimate step is the isomerization of
2-cyclohexenylcarbonyl-CoA to 1-cyclohexenylcarbonyl-CoA. We have purified a 28
kDa 2-cyclohexenylcarbonyl-CoA isomerase (ChcB) from S. collinus and cloned and
sequenced the corresponding chcB gene. The predicted amino acid sequence of ChcB
showed moderate sequence identity to members of the hydratase/isomerase
superfamily of enzymes. The recombinant ChcB was overexpressed in Escherichia
coli and purified to homogeneity using metal chelate chromatography. Kinetic
analysis demonstrated that recombinant ChcB had wide substrate specificity and
could catalyze a double bond isomerization using 2-cyclohexenylcarbonyl-CoA (K(m)
116 +/- 68 microM, k(cat)( )()3.7 +/- 1.0 min(-)(1)), trans-3-hexenyl-CoA (K(m)
39 +/- 10 microM, k(cat)( )()12.8 +/- 1 min(-)(1)), and vinylacetyl-CoA (K(m) 156
+/- 34 microM, k(cat)( )()29 +/- 3 min(-)(1)) as substrates. ChcB activity in
cell extracts of S. collinus SP1, an insertionally disrupted chcB mutant, was
shown to decrease by more than 99% (as compared to the wild-type strain) using
all three of these substrates. The S. collinus SP1 strain, unlike the wild-type
strain, could not produce omega-cyclohexyl fatty acids but was still able to grow
efficiently on methyl oleate as a sole carbon source. These observations
demonstrate that the S. collinus ChcB is required for catalyzing the
isomerization of 2-cyclohexenylcarbonyl-CoA to 1-cyclohexenylcarbonyl-CoA during
CHC-CoA biosynthesis but not for degradation of unsaturated fatty acids. The chcB
gene does not appear to be associated with the ansatrienin biosynthetic gene
cluster, which has previously been shown to contain at least one gene known to be
essential for CHC-CoA biosynthesis. This finding represents a notable exception
to the general rule regarding the clustering of polyketide biosynthetic pathway
genes.
<br><br>
2. J Nat Prod. 1994 Mar;57(3):382-6.
<br><br>
Biosynthetic studies on the origin of the cyclohexanecarboxylic acid moiety of
ansatrienin A and omega-cyclohexyl fatty acids.
<br>
Moore BS(1), Floss HG.
<br>
Author information: <br>
(1)Department of Chemistry, University of Washington, Seattle 98195.
<br>
Feeding experiments with [2,6,10,10-2H4]chorismate in Streptomyces collinus
(ansatrienin A) and Alicyclobacillus acidocaldarius (omega-cyclohexyl fatty
acids), and inhibitor experiments with glyphosate in the latter organism, have
shown that the biosynthesis of cyclohexanecarboxylic acid branches off from the
shikimate pathway at a point prior to enolpyruvylshikimate 3-phosphate, either at
shikimate or shikimate 3-phosphate.<br>
|
