Disease relevance of dl-Dithiobiotin

• Two steps in the biosynthesis of biotin in Escherichia coli, incorporation of the nitrogen atom of methionine into 7-keto-8-aminopelargonic acid and of the sulfur atom into dethiobiotin, were examined [1].
• Biosynthesis of biotin from dethiobiotin by the biotin auxotroph Lactobacillus plantarum [2].

High impact information on dl-Dithiobiotin

• Biotin synthase (BioB) catalyzes the insertion of a sulfur atom between the C6 and C9 carbons of dethiobiotin [3].
• The C53S, C57S, and C60S mutant proteins, both as prepared and reconstituted, were unable to covert dethiobiotin to biotin in vitro and in vivo [4].
• Biotin synthase is required for the conversion of dethiobiotin to biotin and requires a number of accessory proteins and small molecule cofactors for activity in vitro [5].
• A first radical formed on dethiobiotin is trapped by the sulfur donor, which was found to be the iron-sulfur (Fe-S) center contained in the enzyme, and cyclization follows in a second step [6].
• Biotin synthase (BS) is an AdoMet-dependent radical enzyme that catalyzes the insertion of sulfur into saturated C6 and C9 atoms in the substrate dethiobiotin [7].

Chemical compound and disease context of dl-Dithiobiotin

• Further investigation on the turnover of Escherichia coli biotin synthase with dethiobiotin and 9-mercaptodethiobiotin as substrates [8].
• The crystal structure of biotin synthase from Escherichia coli in complex with S-adenosyl-L-methionine and dethiobiotin has been determined to 3.4 angstrom resolution [9].

Biological context of dl-Dithiobiotin

• Biotin synthetase (BS) catalyses the biotransformation of dethiobiotin (DTB) to biotin [10].
• On the mechanism of conversion of dethiobiotin to biotin in Escherichia coli. Discussion of the occurrence of an intermediate hydroxylation [11].
• The plasmid pUCBIO2 containing the yeast BIO2 gene completely complements E. coli bioB- and delta bio mutants and enables these mutants to grow on dethiobiotin [12].
• Deletion analysis of the biotin operon indicated that overexpression of the bioB gene alone, the product of which is believed to catalyze the conversion of dethiobiotin to biotin, is sufficient for growth inhibition [13].

Anatomical context of dl-Dithiobiotin

• Diaminobiotin and desthiobiotin have biotin-like activities in Jurkat cells [14].

Associations of dl-Dithiobiotin with other chemical compounds

• Biotin synthase is an iron-sulfur protein that utilizes AdoMet to catalyze the presumed radical-mediated insertion of a sulfur atom between the saturated C6 and C9 carbons of dethiobiotin [15].
• Dethiobiotin synthetase (DTBS) catalyzes the penultimate step in biotin biosynthesis, the formation of the ureido ring of dethiobiotin from (7R,8S)-7,8-diaminononanoic acid (7,8-diaminopelargonic acid, DAPA), CO2, and ATP [16].
• Biotin and the internal standard dethiobiotin are converted into fluorescent derivatives by using panacyl bromide [p-(9-anthroyloxy)phenacyl bromide] as a fluorescence label [17].
• R.I.-K(biotin)-Tat9 transport in Caco-2 and CHO/hSMVT cells was significantly inhibited by known substrates of SMVT including biotin, biocytin, and desthiobiotin [18].

Gene context of dl-Dithiobiotin

• The OK2 strain would only cross-feed with the Escherichia coli bioB mutant and also grew well in medium containing dethiobiotin [19].
• To investigate the conversion of dethiobiotin to biotin in the plant kingdom, the cDNA encoding the bioB gene product equivalent from Arabidopsis thaliana was used to construct an E. coli overexpression strain [20].
• We have reported [Ifuku, O., Kishimoto, J., Haze, S., Yanagi, M. & Fukushima, S. (1992) Biosci. Biotechnol. Biochem. 56, 1780-1785] the enzymic conversion of dethiobiotin to biotin (catalyzed by the enzyme encoded by bioB) in cell-free extract of Escherichia coli which had been genetically engineered for high bioB expression [21].
• Flavodoxin is required for conversion of dethiobiotin to biotin in Escherichia coli [21].

Analytical, diagnostic and therapeutic context of dl-Dithiobiotin

• The first two steps of dethiobiotin formation, which is a complex, multistep enzymatic reaction, have been elucidated by a combination of X-ray crystallography and kinetic methods [22].

References