BCII: Fatty Acid Biosynthesis Flashcards | Quizlet

Fatty acid biosynthesis is NOT just a reversal of β ..

Fatty Acid Bio Synthesis | Biosynthesis | Metabolism

In this reaction a carboxyl group is added to acetyl CoA to generate malonyl CoA. This biotin-containing enzyme catalyzes the committed step in fatty acid biosynthesis and is subject to a complex regulation not covered in this activity.

The first committed step in fatty acid biosynthesis is ..

Bio Synthesis of Fatty Acids | Ketosis | Fatty Acid

In most bacteria the last step in synthesis of the pimelate moiety of biotin is cleavage of the ester bond of pimeloyl-acyl carrier protein (ACP) methyl ester. The paradigm cleavage enzyme is Escherichia coli BioH which together with the BioC methyltransferase allows synthesis of the pimelate moiety by a modified fatty acid biosynthetic pathway. Analyses of the extant bacterial genomes showed that bioH is absent from many bioC-containing bacteria and is replaced by other genes. Helicobacter pylori lacks a gene encoding a homologue of the known pimeloyl-ACP methyl ester cleavage enzymes suggesting that it encodes a novel enzyme that cleaves this intermediate. We isolated the H. pylori gene encoding this enzyme, bioV, by complementation of an E. coli bioH deletion strain. Purified BioV cleaved the physiological substrate, pimeloyl-ACP methyl ester to pimeloyl-ACP by use of a catalytic triad, each member of which was essential for activity. The role of BioV in biotin biosynthesis was demonstrated using a reconstituted in vitro desthiobiotin synthesis system. BioV homologues seem the sole pimeloyl-ACP methyl ester esterase present in the Helicobacter species and their occurrence only in H. pylori and close relatives provide a target for development of drugs to specifically treat Helicobacter infections.

N2 - In most bacteria the last step in synthesis of the pimelate moiety of biotin is cleavage of the ester bond of pimeloyl-acyl carrier protein (ACP) methyl ester. The paradigm cleavage enzyme is Escherichia coli BioH which together with the BioC methyltransferase allows synthesis of the pimelate moiety by a modified fatty acid biosynthetic pathway. Analyses of the extant bacterial genomes showed that bioH is absent from many bioC-containing bacteria and is replaced by other genes. Helicobacter pylori lacks a gene encoding a homologue of the known pimeloyl-ACP methyl ester cleavage enzymes suggesting that it encodes a novel enzyme that cleaves this intermediate. We isolated the H. pylori gene encoding this enzyme, bioV, by complementation of an E. coli bioH deletion strain. Purified BioV cleaved the physiological substrate, pimeloyl-ACP methyl ester to pimeloyl-ACP by use of a catalytic triad, each member of which was essential for activity. The role of BioV in biotin biosynthesis was demonstrated using a reconstituted in vitro desthiobiotin synthesis system. BioV homologues seem the sole pimeloyl-ACP methyl ester esterase present in the Helicobacter species and their occurrence only in H. pylori and close relatives provide a target for development of drugs to specifically treat Helicobacter infections.


Fatty acid biosynthesis - ScienceDirect

This enzyme is one of the most complex in our bodies. It consists of three polypeptide chains, two of which are identical to each other. The third is a very small polypeptide called acyl carrier protein (ACP), which contains a phosphopantetheine group (derived from the vitamin panthothenic acid) that is identical to the one in Coenzyme A. The other two polypeptides have 7 different enzymatic activities. The enzyme works by first mobilizing malonyl CoA and acetyl CoA (attaching them to ACP). Then the enzyme begins a cycle of reactions in which a fatty acid grows from ACP. At the end of each cycle the growing fatty acid is 2 carbons long. When the fatty acid has reached 16 carbons in length, it is cleaved from the ACP.

121 Fatty Acid Biosynthesis example was ..

The conundrum is how to assemble a seven-carbon dicarboxylic acid in E. coli. Genetic analyses implicate only two genes, bioC and bioH, in pimeloyl moiety synthesis, but neither gene product appears able to play a direct role in assembling the carbon chain. BioC is annotated as an S-adenosyl-L-methionine (SAM)-dependent methyltransferase whereas BioH has been shown to have esterase activity on short and medium chain acyl p-nitrophenyl esters and on the methyl ester of dimethylbutyryl-S-methyl mercaptopropionate. The BioC annotation was especially puzzling because all of the pimeloyl moiety carbon atoms are derived from acetate and CO2,. The remaining bio genes encode enzymes that function late in the pathway and thus it seemed that assembly of the pimeloyl moiety must require additional enzymes belonging to another biosynthetic pathway that are somehow assisted in this task by BioC and BioH. In 196 a pathway was proposed in which pimeloyl-CoA synthesis could be formed by the enzymes of fatty acid synthesis. The proposal was that three malonyl-CoA molecules would be condensed with the primer malonyl moiety retaining the carboxyl group introduced by acetyl-CoA carboxylase fixation of CO2. The other two malonyl-CoA molecules would lose their free carboxyl groups in the course of the two decarboxylative Claisen reactions required to give the C7 dicarboxylate, a scheme consistent with the 13C labeling studies and the precedent of type III polyketide synthases,. However, in fatty acid synthesis the growing chains are attached to ACP rather than CoA and unlike polyketides, where the keto groups are either retained or consumed in rearrangements of the carbon chain (e.g., cyclization), pimelate synthesis requires that the keto groups be converted to methylene groups. Although the enzymes of fatty acid synthesis could in principle perform this conversion, it seemed most unlikely that the fatty acid synthetic enzymes could accept substrates having a carboxyl group in place of the usual terminal methyl group because the fatty acid synthetic enzymes sequester the growing fatty acyl chains in strongly hydrophobic tunnels or clefts. It occurred to us that BioC and BioH could circumvent this conundrum.

In yeast, fatty acid biosynthesis is terminated with the ..

In our model () the role of BioC is to convert the free carboxyl group of a malonyl-thioester to its methyl ester by transfer of a methyl group from SAM. Methylation would both cancel the charge of the carboxyl group and provide a methyl carbon to mimic the methyl ends of normal fatty acyl chains. The esterified malonyl-thioester would enter the fatty acid synthetic pathway as in the 1963 proposal. Two reiterations of the elongation cycle would produce pimeloyl-ACP methyl ester. BioH would then cleave the methyl ester to give pimeloyl-ACP which BioF would utilize to make 7-keto-8-aminopelargonic acid (KAPA), the first intermediate in biotin ring assembly. In this scenario, introduction of the methyl ester disguises the biotin synthetic intermediates such that they become substrates for the fatty acid synthetic pathway. When synthesis of the pimeloyl moiety is complete and disguise is no longer needed, the methyl group is removed to free the carboxyl group that will eventually be used to attach biotin to its cognate metabolic enzymes. We report that the monomethyl esters of malonic, glutaric and pimelic acid allow growth of a ΔbioC strain in the absence of biotin, but fail to allow growth of ΔbioC ΔbioH strains. An in vitro system was developed in which dialyzed cell extracts converted malonyl-CoA to dethiobiotin (DTB, the last intermediate of the pathway) which defined the proposed pathway by allowing the precursor requirements of the pathway and the effects of inhibitors of fatty acid synthesis and methyl transfer on DTB synthesis to be determined.