Sirota FL

Functional Classification of Super-Large Families of Enzymes Based on Substrate Binding Pocket Residues for Biocatalysis and Enzyme Engineering Applications

Large enzyme families such as the groups of zinc-dependent alcohol dehydrogenases (ADHs), long chain alcohol oxidases (AOxs) or amine dehydrogenases (AmDHs) with, sometimes, more than one million sequences in the non-redundant protein database and hundreds of experimentally characterized enzymes are excellent cases for protein engineering efforts aimed at refining and modifying substrate specificity.

Read

Factors influencing SARS-CoV-2 transmission and outbreak control measures in densely populated settings

Starting with a handful of SARS-CoV-2 infections in dormitory residents in late March 2020, rapid transmission in their dense living environments ensued and by October 2020, more than 50,000 acute infections were identified across various dormitories in Singapore.

Read

Loss of C2orf69 defines a fatal autoinflammatory syndrome in humans and zebrafish that evokes a glycogen-storage-associated mitochondriopathy

Human C2orf69 is an evolutionarily conserved gene whose function is unknown. Here, we report eight unrelated families from which 20 children presented with a fatal syndrome consisting of severe autoinflammation and progredient leukoencephalopathy with recurrent seizures; 12 of these subjects, whose DNA was available, segregated homozygous loss-of-function C2orf69 variants.

Read

Loss of C2orf69 defines a fatal autoinflammatory syndrome in humans and zebrafish that evokes a glycogen-storage-associated mitochondriopathy

Human C2orf69 is an evolutionarily conserved gene whose function is unknown. Here, we report eight unrelated families from which 20 children presented with a fatal syndrome consisting of severe autoinflammation and progredient leukoencephalopathy with recurrent seizures; 12 of these subjects, whose DNA was available, segregated homozygous loss-of-function C2orf69 variants.

Read

Conserved sequence motifs in human TMTC1, TMTC2, TMTC3, and TMTC4, new Omannosyltransferases from the GT-C/PMT clan, are rationalized as ligand binding sites

The human proteins TMTC1, TMTC2, TMTC3 and TMTC4 have been experimentally shown to be components of a new O-mannosylation pathway. Their own mannosyl-transferase activity has been suspected but their actual enzymatic potential has not been demonstrated yet. So far, sequence analysis of TMTCs has been compromised by evolutionary sequence divergence within their membrane-embedded N-terminal region, sequence inaccuracies in the protein databases and the difficulty to interpret the large functional variety of known homologous proteins (mostly sugar transferases and some with known 3D structure).

Read

Identification and engineering of 32 membered antifungal macrolactone notonesomycins

Notonesomycin A is a 32-membered bioactive glycosylated macrolactone known to be produced by Streptomyces aminophilus subsp. notonesogenes 647-AV1 and S. aminophilus DSM 40186. In a high throughput antifungal screening campaign, we identified an alternative notonesomycin A producing strain, Streptomyces sp. A793, and its biosynthetic gene cluster.

Read

The Geographic Variation of Surveillance and Zoonotic Spillover Potential of Influenza Viruses in Domestic Poultry and Swine

Background Avian and swine influenza viruses circulate worldwide and pose threats to both animal and human health. The design of global surveillance strategies is hindered by information gaps on the geospatial variation in virus emergence potential and existing surveillance efforts.

Read

Isolation and Identification of an Anthracimycin Analogue from Nocardiopsis kunsanensis, a Halophile from a Saltern, by Genomic Mining Strategy

Modern medicine is unthinkable without antibiotics; yet, growing issues with microbial drug resistance require intensified search for new active compounds. Natural products generated by Actinobacteria have been a rich source of candidate antibiotics, for example anthracimycin that, so far, is only known to be produced by Streptomyces species.

Read