3 research outputs found
Biosynthesis of the Azoxy Compound Azodyrecin from <i>Streptomyces mirabilis</i> P8-A2
Azoxy compounds are a distinctive
group of bioactive secondary
metabolites characterized by a unique RNN+(O–)R moiety. The azoxy moiety is present in various classes
of metabolites that exhibit various biological activities. The enzymatic
mechanisms underlying azoxy bond formation remain enigmatic. Azodyrecins
are cytotoxic azoxy metabolites produced by Streptomyces mirabilis P8-A2. Here, we cloned and confirmed the putative azd biosynthetic gene cluster through CATCH cloning followed by expression
and production of azodyrecins in two heterologous hosts, S.
albidoflavus J1074 and S. coelicolor M1146,
respectively. We explored the function of 14 enzymes in azodyrecin
biosynthesis through gene knockout using CRISPR-Cas9 base editing
in the native producer, S. mirabilis P8-A2. The key
intermediates were analyzed in the mutants through MS/MS fragmentation
studies, revealing azoxy bond formation via the conversion of hydrazine
to an azo compound followed by further oxygenation. Enzymes involved
in modifications of the precursor could be postulated based on their
predicted function and the intermediates identified in the knockout
strains. Moreover, the distribution of the azoxy biosynthetic gene
clusters across Streptomyces spp. genomes is explored,
highlighting the presence of these clusters in over 20% of the Streptomyces spp. genomes and revealing that azoxymycin
and valanimycin are scarce, while azodyrecin and KA57A-like clusters
are widely distributed across the phylogenetic tree
An individual with Sarmatian-related ancestry in Roman Britain.
In the second century CE the Roman Empire had increasing contact with Sarmatians, nomadic Iranian speakers occupying an area stretching from the Pontic-Caspian steppe to the Carpathian mountains, both in the Caucasus and in the Danubian borders of the empire.1,2,3 In 175 CE, following their defeat in the Marcomannic Wars, emperor Marcus Aurelius drafted Sarmatian cavalry into Roman legions and deployed 5,500 Sarmatian soldiers to Britain, as recorded by contemporary historian Cassius Dio.4,5 Little is known about where the Sarmatian cavalry were stationed, and no individuals connected with this historically attested event have been identified to date, leaving its impact on Britain largely unknown. Here we document Caucasus- and Sarmatian-related ancestry in the whole genome of a Roman-period individual (126-228 calibrated [cal.] CE)-an outlier without traceable ancestry related to local populations in Britain-recovered from a farmstead site in present-day Cambridgeshire, UK. Stable isotopes support a life history of mobility during childhood. Although several scenarios are possible, the historical deployment of Sarmatians to Britain provides a parsimonious explanation for this individual's extraordinary life history. Regardless of the factors behind his migrations, these results highlight how long-range mobility facilitated by the Roman Empire impacted provincial locations outside of urban centers
Detection of chromosomal aneuploidy in ancient genomes.
Ancient DNA is a valuable tool for investigating genetic and evolutionary history that can also provide detailed profiles of the lives of ancient individuals. In this study, we develop a generalised computational approach to detect aneuploidies (atypical autosomal and sex chromosome karyotypes) in the ancient genetic record and distinguish such karyotypes from contamination. We confirm that aneuploidies can be detected even in low-coverage genomes ( ~ 0.0001-fold), common in ancient DNA. We apply this method to ancient skeletal remains from Britain to document the first instance of mosaic Turner syndrome (45,X0/46,XX) in the ancient genetic record in an Iron Age individual sequenced to average 9-fold coverage, the earliest known incidence of an individual with a 47,XYY karyotype from the Early Medieval period, as well as individuals with Klinefelter (47,XXY) and Down syndrome (47,XY, + 21). Overall, our approach provides an accessible and automated framework allowing for the detection of individuals with aneuploidies, which extends previous binary approaches. This tool can facilitate the interpretation of burial context and living conditions, as well as elucidate past perceptions of biological sex and people with diverse biological traits