Biosynthesis-driven structure-activity relationship study of premonensin-derivatives.

The controlled derivatization of natural products is of great importance for their use in drug discovery. The ideally rapid generation of compound libraries for structure-activity relationship studies is of particular concern. We here use modified biosynthesis for the generation of such a library of reduced polyketides to interfere with the oncogenic KRas pathway. The polyketide is derivatized via side chain alteration, and variations in its redox pattern and in its backbone chain length through manipulation in the corresponding polyketide synthase. Structural and biophysical analyses revealed the nature of the interaction between the polyketides and KRas-interacting protein PDE6δ. Non-natural polyketides with low nanomolar affinity to PDE6δ were identified.

Patterns of genetic and eco-geographical diversity in Spanish barleys.

The pool of Western Mediterranean landraces has been under-utilised for barley breeding so far. The objectives of this study were to assess genetic diversity in a core collection of inbred lines derived from Spanish barley landraces to establish its relationship to barleys from other origins, and to correlate the distribution of diversity with geographical and climatic factors. To this end, 64 SSR were used to evaluate the polymorphism among 225 barley (Hordeum vulgare ssp. vulgare) genotypes, comprising two-row and six-row types. These included 159 landraces from the Spanish barley core collection (SBCC) plus 66 cultivars, mainly from European countries, as a reference set. Out of the 669 alleles generated, a large proportion of them were unique to the six-row Spanish barleys. An analysis of molecular variance revealed a clear genetic divergence between the six-row Spanish barleys and the reference cultivars, whereas this was not evident for the two-row barleys. A model-based clustering analysis identified an underlying population structure, consisting of four main populations for the whole genotype set, and suggested further possible subdivision within two of these populations. Most of the six-row Spanish landraces clustered into two groups that corresponded to geographic regions with contrasting environmental conditions. The existence of wide genetic diversity in Spanish germplasm, possibly related to adaptation to a broad range of environmental conditions, and its divergence from current European cultivars confirm its potential as a new resource for barley breeders, and make the SBCC a valuable tool for the study of adaptation in barley.

Distribution of MWG699 polymorphism in Spanish European barleys.

The STS marker MWG699/TaqI is closely linked to the vrs1 locus and has been proposed as a marker of domestication in barley. This study included 257 cultivated barleys of both two- and six-rowed varieties, mainly from the western Mediterranean region. These included many landraces from the Spanish barley core collection, Moroccan landraces, and a set of accessions from other European countries. Restriction analysis of amplified DNA revealed three alleles, as previously described. Most of the two-rowed entries had the same allele, type K. Six-rowed entries showed both types A and D. Indeed, type D was widespread among Spanish landraces and commercial varieties from central Europe. It was also found in some two-rowed landraces originating from Spain and Morocco. Barleys with the D haplotype were predominantly winter types, whereas the A haplotype was evenly distributed among spring and winter types. These results support the existence of two different genetic sources among six-rowed Spanish landraces.