Alternative pathways for biosynthesis of leucine and other amino acids in Bacteroides ruminicola and Bacteroides fragilis.
Bacteroides ruminicola is one of several species of anaerobes that are able to reductively carboxylate isovalerate (or isovaleryl-coenzyme A) to synthesize alpha-ketoisocaproate and thus leucine. When isovalerate was not supplied to growing B. ruminicola cultures, carbon from [U-14C]glucose was used for the synthesis of leucine and other cellular amino acids. When unlabeled isovalerate was available, however, utilization of [U-14C]glucose or [2-14C]acetate for leucine synthesis was markedly and specifically reduced. Enzyme assays indicated that the key enzyme of the common isopropylmalate (IPM) pathway for leucine biosynthesis, IPM synthase, was present in B. ruminicola cell extracts. The specific activity of IPM synthase was reduced when leucine was added to the growth medium but was increased by the addition of isoleucine plus valine, whereas the addition of isovalerate had little or no effect. The activity of B. ruminicola IPM synthase was strongly inhibited by leucine, the end product of the pathway. It seems unlikely that the moderate inhibition of the enzyme by isovalerate adequately explains the regulation of carbon flow by isovalerate in growing cultures. Bacteroides fragilis apparently also uses either the isovalerate carboxylation or the IPM pathway for leucine biosynthesis. Furthermore, both of these organisms synthesize isoleucine and phenylalanine, using carbon from 2-methylbutyrate and phenylacetate, respectively, in preference to synthesis of these amino acids de novo from glucose. Thus, it appears that these organisms have the ability to regulate alternative pathways for the biosynthesis of certain amino acids and that pathways involving reductive carboxylations are likely to be favored in their natural habitats.
D015079:2-Isopropylmalate Synthase / Q000032:analysis; D000596:Amino Acids / Q000096:biosynthesis*; D000818:Animals; D001439:Bacteroides / Q000378:metabolism*; D001441:Bacteroides fragilis / Q000378:metabolism*; D002245:Carbon Dioxide / Q000378:metabolism; D002250:Carbon Radioisotopes; D045782:Hemiterpenes; D007930:Leucine / Q000096:biosynthesis*; D010421:Pentanoic Acids / Q000378:metabolism; D012417:Rumen / Q000382:microbiology
D000596:Amino Acids; D002250:Carbon Radioisotopes; D045782:Hemiterpenes; D010421:Pentanoic Acids; D002245:Carbon Dioxide; C008216:isovaleric acid; D015079:2-Isopropylmalate Synthase; D007930:Leucine