fatty acids. 5 Micro-organisms, plants and some fungi are able to syn-
thesize biotin de novo as well as importing it from their environment
through the action of a biotin transport system. In contrast, humans
and other mammals are biotin auxotrophs and rely solely on uptake
from external sources, such as intestinal microflora or the diet. 6 This
genetic difference in biotin metabolism between humans and mi-
crobes provides potential drug targets for new antibiotic discovery
(reviewed 7 ). The biotin synthesis pathway is well characterized in
E. coli and Bacillus subtilis and has recently been reviewed. 8 In many
bacteria the genes that encode the biotin biosynthetic enzymes are
often clustered into an operon known as the bio operon. 9 Briefly,
the synthetic pathway commences with L-alanine and S-adenosyl-
L- methionine being introduced into pimeloyl-ACP by the activities
of 7-keto-8-aminopelargonic acid synthase (encoded by bioF) and
7,8-diaminopelargonic acid synthase (encoded by bioA), respec-
tively, to generate 7,8-diaminopelargonic acid. Dethiobiotin
synthetase (encoded by bioD) and biotin synthase (encoded by bioB)
then catalyze the closure of the ureido and thiophane hetero-
cycles, respectively, liberating biotin.
The de novo synthesis of biotin is metabolically costly, requir-
ing 20 equivalents of ATP for each molecule of biotin and the
activities of at least 4 metabolic enzymes. 10 Therefore, transcrip-
tional regulation of the biotin biosynthetic enzymes needs to be
fatty acids. 5 Micro-organisms, plants and some fungi are able to syn-thesize biotin de novo as well as importing it from their environmentthrough the action of a biotin transport system. In contrast, humansand other mammals are biotin auxotrophs and rely solely on uptakefrom external sources, such as intestinal microflora or the diet. 6 Thisgenetic difference in biotin metabolism between humans and mi-crobes provides potential drug targets for new antibiotic discovery(reviewed 7 ). The biotin synthesis pathway is well characterized inE. coli and Bacillus subtilis and has recently been reviewed. 8 In manybacteria the genes that encode the biotin biosynthetic enzymes areoften clustered into an operon known as the bio operon. 9 Briefly,the synthetic pathway commences with L-alanine and S-adenosyl-L- methionine being introduced into pimeloyl-ACP by the activitiesof 7-keto-8-aminopelargonic acid synthase (encoded by bioF) and7,8-diaminopelargonic acid synthase (encoded by bioA), respec-tively, to generate 7,8-diaminopelargonic acid. Dethiobiotinsynthetase (encoded by bioD) and biotin synthase (encoded by bioB)then catalyze the closure of the ureido and thiophane hetero-cycles, respectively, liberating biotin.The de novo synthesis of biotin is metabolically costly, requir-ing 20 equivalents of ATP for each molecule of biotin and theactivities of at least 4 metabolic enzymes. 10 Therefore, transcrip-tional regulation of the biotin biosynthetic enzymes needs to be
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