Mechanisms of biotin-regulated gene expression in microbes

Abstract

Biotin is an essential micronutrient that acts as a co-factor for biotin-dependent metabolic enzymes. In bacteria, the supply of biotin can be achieved by de novo synthesis or import from exogenous sources. Certain bacteria are able to obtain biotin through both mechanisms while others can only fulfill their biotin requirement through de novo synthesis. Inability to fulfill their cellular demand for biotin can have detrimental consequences on cell viability and virulence. Therefore understanding the transcriptional mechanisms that regulate biotin biosynthesis and transport will extend our knowledge about bacterial survival and metabolic adaptation during pathogenesis when the supply of biotin is limited. The most extensively characterized protein that regulates biotin synthesis and uptake is BirA. In certain bacteria, such as Escherichia coli and Staphylococcus aureus, BirA is a bi-functional protein that serves as a transcriptional repressor to regulate biotin biosynthesis genes, as well as acting as a ligase to catalyze the biotinylation of biotin-dependent enzymes. Recent studies have identified two other proteins that also regulate biotin synthesis and transport, namely BioQ and BioR. This review summarizes the different transcriptional repressors and their mechanism of action. Moreover, the ability to regulate the expression of target genes through the activity of a vitamin, such as biotin, may have biotechnological applications in synthetic biology.

Comparative genomics of the genus Roseburia reveals divergent biosynthetic pathways that may influence colonic competition among species

“…Biotin is required as a cofactor central to carboxyl group transfer [119] and is involved in pyruvate interconversion with oxaloacetate as well as amino acid, fatty acid and urea metabolism (via urea carboxylase), among other pathways [18]. Biotin synthesis is a tightly regulated and energetically costly process [120], and we only found evidence for synthesis from pimelate thioester in the R. intestinalis genomes studied here.…”

Phylogenomics suggests oxygen availability as a driving force in Thaumarchaeota evolution

“…The ability to synthesize vitamins B 1 , B 2 , B 6 , and B 12 has been demonstrated in several pure cultures of the marine AOA of the genus Nitrosopumilus [56,57], and the genes for biotin synthesis were shown to be functional in Candidatus Nitrososphaera gargensis [58]. Vitamins are often used as cofactors in some enzymes, including biotindependent enzymes such as acetyl-CoA/propionyl-CoA carboxylase [59,60] and cobalamin-dependent enzymes such as methionine synthase (metH), methylmalony-CoA mutase (mut), and ribonucleotide reductase (rnr) [61]. Among these, acetyl-CoA/propionyl-CoA carboxylase and methylmalony-CoA mutase are known to be associated with inorganic carbon fixation via the autotrophic hydroxypropionate/hydroxybutyrate (HP/HB) cycle [62], which has been shown to be highly energy-efficient in the presence of oxygen in N. maritimus SCM1 [63].…”

The DEAD-box RNA helicase CshA is required for fatty acid homeostasis in Staphylococcus aureus

“…Moreover, we identified three mutations located in genes involved in biotin synthesis or uptake pathways ( Table 1 ), with two mutations in birA , encoding the bifunctional biotin ligase and transcriptional repressor, and one in bioY , the substrate-specific S component of the biotin ECF transporter [ 24 ]. Since biotin is a cofactor of the ACC complex, we determined whether its activity is also affected by these mutations using the same read-out than above.…”