title: Remarkable diversity in the enzymes catalyzing the last step in synthesis of the pimelate moiety of biotin.
abstract: Biotin synthesis in Escherichia coli requires the functions of the bioH and bioC genes to synthesize the precursor pimelate moiety by use of a modified fatty acid biosynthesis pathway. However, it was previously noted that bioH has been replaced with bioG or bioK within the biotin synthetic gene clusters of other bacteria. We report that each of four BioG proteins from diverse bacteria and two cyanobacterial BioK proteins functionally replace E. coli BioH in vivo. Moreover, purified BioG proteins have esterase activity against pimeloyl-ACP methyl ester, the physiological substrate of BioH. Two of the BioG proteins block biotin synthesis when highly expressed and these toxic proteins were shown to have more promiscuous substrate specificities than the non-toxic BioG proteins. A postulated BioG-BioC fusion protein was shown to functionally replace both the BioH and BioC functions of E. coli. Although the BioH, BioG and BioK esterases catalyze a common reaction, the proteins are evolutionarily distinct.
authors.affiliation: Department of Microbiology, University of Illinois, Urbana, Illinois, United States of America.
authors.forename: Madelyn M
authors.initials: MM
authors.lastname: Shapiro
authors.forename: Vandana
authors.initials: V
authors.lastname: Chakravartty
authors.forename: John E
authors.initials: JE
authors.lastname: Cronan
mesh_terms: D000595:Amino Acid Sequence; D055162:Biocatalysis; D053898:Biosynthetic Pathways; D001710:Biotin / Q000096:biosynthesis* / Q000737:chemistry; D017124:Conserved Sequence; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics; D004950:Esterases / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D019143:Evolution, Molecular; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial / Q000235:genetics; D006193:Haemophilus influenzae / Q000201:enzymology; D006639:Histidine / Q000378:metabolism; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism; D010802:Phylogeny; D010867:Pimelic Acids / Q000737:chemistry / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016415:Sequence Alignment; D013379:Substrate Specificity
chemical_list: C471213:His-His-His-His-His-His; D009842:Oligopeptides; D010867:Pimelic Acids; D011993:Recombinant Fusion Proteins; D006639:Histidine; D001710:Biotin; D004950:Esterases