Volume 8 Issue 10, October 2012

By incorporating sequence homology and context associations, global probabilistic approaches to annotate genome-scale metabolic networks can substantially improve the accuracy of biochemical predictions, revealing potential functionality and directing experimental validation.

The phospholipid-lysophospholipid transacylase tafazzin is responsible for enrichment of the cardiolipin fraction of mitochondria with tetralinoleoyl-cardiolipin. The specificity for linoleoyl hydrocarbon chains is now explained by the specific action of tafazzin on negatively curved lipid monolayers.

Bacterial persisters consist of a phenotypic subpopulation that survives antibiotic treatment, prolonging infection. The GhoT toxin from the newly discovered ghoS-ghoT toxin-antitoxin system contributes to persistence, most likely by interfering with bacterial inner membrane integrity.

The mechanism for nitro group formation in the thaxtomin family of natural products is unknown. Genetic and biochemical studies now show the cytochrome P450 TxtE catalyzes this direct and regioselective nitration, using NO and O₂ to modify a tryptophan indole ring.

DNA damage products influence DNA replication but also may induce stalling or mutagenesis during transcription. A competitive transcription and adduct bypass assay provides a new approach for assessing the transcriptional effects of DNA lesions and links transcriptional arrest of several lesions to nucleotide excision repair pathways.

The reconstitution of two fungal NRPSs provides the first biochemical evidence that these assembly lines use a condensation-like domain to complete the synthesis of cyclic natural products instead of the thioesterase domain used in bacterial species.

C₁₈-ceramide mediates lethal autophagy by anchoring LC3B-II (lipidated LC3) to mitochondrial membranes during mitochondrial fission and thereby recruiting autophagosomes.

A small-molecule activator specific for PKM2 binds to a site distinct from the endogenous activator fructose-1,6-bisphosphate, promoting tetramerization and constitutive activation of PKM2, to inhibit xenograft tumor growth in mice.

A new global annotation strategy combines sequence identity and genomic context to provide probabilities for all metabolic assignments in a given species. Application of this method leads to multiple new annotations and validation of three enzymatic activities in B. subtilis.

Expanding the bacterial toxin-antitoxin system classes to a fifth class, GhoST was found to be involved in maintenance of persister cells, dormant cells that are tolerant of antibiotics. GhoS is the antitoxin, an endoribonuclease that cleaves the toxin mRNA ghoT, whose gene product is a membrane-lytic protein.

Tafazzin, the mitochondrial transacylase that is deficient in Barth syndrome, selects lipid substrates in the inverted hexagonal phase but does not react with bilayer lipids.