The biosynthesis of monensin-A: thymine, beta-aminoisobutyrate and methacrylate metabolism in Streptomyces cinnamonensis.
Feeding experiments with isotopically labelled samples of [13C,2H3-methyl]-thymine, (R,S)-[I-13C]- and (R,S-[13C-methyl]-beta-aminoisobutyrates into monensin-A demonstrate that these metabolites can all contribute to the methylmalonyl-CoA pool in Streptomyces cinnamonensis, and implicate DNA catabolism as a contributory metabolic source of propionate carbon atoms for secondary metabolic biosynthesis. Further, these labelled compounds were unexpectedly incorporated into the butyrate unit of monensin-A, an observation which can be rationalised if beta-aminoisobutyrate is converted to methacrylyl-CoA and then reduced to isobutyryl-CoA prior to conversion to butyryl-Coa by the action of isobutyryl-CoA mutase. Feeding experiments with [I-13C]- and [13C-methyl]-methacrylates and [3-13C]-isobutyrate suggest that these metabolites partition similarly between the butyrate and propionate units of monensin-A consistent with the view that isobutyryl-CoA and methacrylyl-CoA have a close metabolic relationship.
O'Hagan
D
D
Department of Chemistry, University of Durham, United Kingdom.
Rogers
S V
SV
Duffin
G R
GR
Reynolds
K A
KA
D000214:Acyl Coenzyme A / Q000378:metabolism; D000621:Aminoisobutyric Acids / Q000378:metabolism*; D002247:Carbon Isotopes; D004269:DNA, Bacterial / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008689:Methacrylates / Q000378:metabolism*; D008985:Monensin / Q000096:biosynthesis* / Q000737:chemistry; D011422:Propionates / Q000378:metabolism; D013302:Streptomyces / Q000378:metabolism*; D013941:Thymine / Q000378:metabolism*
D000214:Acyl Coenzyme A; D000621:Aminoisobutyric Acids; D002247:Carbon Isotopes; D004269:DNA, Bacterial; D008689:Methacrylates; D011422:Propionates; C015357:methylmalonyl-coenzyme A; C050106:isobutyryl-coenzyme A; C008384:methacrylic acid; C024343:butyryl-coenzyme A; D008985:Monensin; C029658:propionic acid; D013941:Thymine; C033435:3-aminoisobutyric acid