10 research outputs found
Cyclofaulknamycin with the Rare Amino Acid D-capreomycidine Isolated from a Well-Characterized Streptomyces albus Strain
Targeted genome mining is an efficient method of biosynthetic gene cluster prioritization
within constantly growing genome databases. Using two capreomycidine biosynthesis genes, alphaketoglutarate-dependent arginine beta-hydroxylase and pyridoxal-phosphate-dependent aminotransferase, we identified two types of clusters: one type containing both genes involved in the
biosynthesis of the abovementioned moiety, and other clusters including only arginine hydroxylase.
Detailed analysis of one of the clusters, the flk cluster from Streptomyces albus, led to the identification
of a cyclic peptide that contains a rare D-capreomycidine moiety for the first time. The absence
of the pyridoxal-phosphate-dependent aminotransferase gene in the flk cluster is compensated by
the XNR_1347 gene in the S. albus genome, whose product is responsible for biosynthesis of the
abovementioned nonproteinogenic amino acid. Herein, we report the structure of cyclofaulknamycin
and the characteristics of its biosynthetic gene cluster, biosynthesis and bioactivity profile
Miramides A–D : Identification of Detoxin-like Depsipeptides after Heterologous Expression of a Hybrid NRPS-PKS Gene Cluster from Streptomyces mirabilis Lu17588
Natural products derived from plants, fungi or bacteria have been used for years in the
medicine, agriculture and food industries as they exhibit a variety of beneficial properties, such
as antibiotic, antifungal, anticancer, herbicidal and immunosuppressive activities. Compared to
synthetic compounds, natural products possess a greater chemical diversity, which is a reason why
they are profitable templates for developing pharmaceutical drug candidates and ongoing research on
them is inevitable. Performing heterologous expression with unknown gene clusters is the preferred
method to activate gene clusters that are not expressed in the wild-type strain under laboratory
conditions; thus, this method offers a way to discover new interesting metabolites. Here, we report the
gene cluster assembly of a hybrid NRPS-PKS gene cluster from Streptomyces mirabilis Lu17588, which
was heterologously expressed in Streptomyces albus Del14. Four new compounds were produced by
the obtained strain, which were named miramides A–D. Isolation and structure elucidation revealed
similarity of the isolated compounds to the known depsipeptides rimosamides/detoxins
Synthesis of 6- or 4-functionalized indoles via a reductive cyclization approach and evaluation as aromatase inhibitors
International audienc
Cyclofaulknamycin with the Rare Amino Acid D-capreomycidine Isolated from a Well-Characterized Strain.
Targeted genome mining is an efficient method of biosynthetic gene cluster prioritization within constantly growing genome databases. Using two capreomycidine biosynthesis genes, alpha-ketoglutarate-dependent arginine beta-hydroxylase and pyridoxal-phosphate-dependent aminotransferase, we identified two types of clusters: one type containing both genes involved in the biosynthesis of the abovementioned moiety, and other clusters including only arginine hydroxylase. Detailed analysis of one of the clusters, the flk cluster from Streptomyces albus, led to the identification of a cyclic peptide that contains a rare D-capreomycidine moiety for the first time. The absence of the pyridoxal-phosphate-dependent aminotransferase gene in the flk cluster is compensated by the XNR_1347 gene in the S. albus genome, whose product is responsible for biosynthesis of the abovementioned nonproteinogenic amino acid. Herein, we report the structure of cyclofaulknamycin and the characteristics of its biosynthetic gene cluster, biosynthesis and bioactivity profile
Loseolamycins: A Group of New Bioactive Alkylresorcinols Produced after Heterologous Expression of a Type III PKS from micromonospora endolithica.
Natural products are a valuable source of biologically active compounds with potential applications in medicine and agriculture. Unprecedented scaffold diversity of natural products and biocatalysts from their biosynthetic pathways are of fundamental importance. Heterologous expression and refactoring of natural product biosynthetic pathways are generally regarded as a promising approach to discover new secondary metabolites of microbial origin. Here, we present the identification of a new group of alkylresorcinols after transcriptional activation and heterologous expression of the type III polyketide synthase of Micromonospora endolithica. The most abundant compounds loseolamycins A1 and A2 have been purified and their structures were elucidated by NMR. Loseolamycins contain an unusual branched hydroxylated aliphatic chain which is provided by the host metabolism and is incorporated as a starter fatty acid unit. The isolated loseolamycins show activity against gram-positive bacteria and inhibit the growth of the monocot weed Agrostis stolonifera in a germination assay. The biosynthetic pathway leading to the production of loseolamycins is proposed in this paper
Miramides A–D: Identification of Detoxin-like Depsipeptides after Heterologous Expression of a Hybrid NRPS-PKS Gene Cluster from Streptomyces mirabilis Lu17588
Natural products derived from plants, fungi or bacteria have been used for years in the medicine, agriculture and food industries as they exhibit a variety of beneficial properties, such as antibiotic, antifungal, anticancer, herbicidal and immunosuppressive activities. Compared to synthetic compounds, natural products possess a greater chemical diversity, which is a reason why they are profitable templates for developing pharmaceutical drug candidates and ongoing research on them is inevitable. Performing heterologous expression with unknown gene clusters is the preferred method to activate gene clusters that are not expressed in the wild-type strain under laboratory conditions; thus, this method offers a way to discover new interesting metabolites. Here, we report the gene cluster assembly of a hybrid NRPS-PKS gene cluster from Streptomyces mirabilis Lu17588, which was heterologously expressed in Streptomyces albus Del14. Four new compounds were produced by the obtained strain, which were named miramides A–D. Isolation and structure elucidation revealed similarity of the isolated compounds to the known depsipeptides rimosamides/detoxins
Synthesis and biological evaluation of 5-[(aryl)(1H-imidazol-1-yl)methyl]-1H-indoles: Potent and selective aromatase inhibitors
International audienc