Fosmidomycin biosynthesis diverges from related phosphonate natural products.

Fosmidomycin and related molecules comprise a family of phosphonate natural products with potent antibacterial, antimalarial and herbicidal activities. To understand the biosynthesis of these compounds, we characterized the fosmidomycin producer, Streptomyces lavendulae, using biochemical and genetic approaches. We were unable to elicit production of fosmidomycin, instead observing the unsaturated derivative dehydrofosmidomycin, which we showed potently inhibits 1-deoxy-D-xylulose-5-phosphate reductoisomerase and has bioactivity against a number of bacteria.

Structural and functional characterisation of the methionine adenosyltransferase from Thermococcus kodakarensis.

Background: Methionine adenosyltransferases catalyse the synthesis of S-adenosylmethionine, a cofactor abundant in all domains of life. In contrast to the enzymes from bacteria and eukarya that show high sequence similarity, methionine adenosyltransferases from archaea diverge on the amino acid sequence level and only few conserved residues are retained.

Results: We describe the initial characterisation and the crystal structure of the methionine adenosyltransferase from the hyperthermophilic archaeon Thermococcus kodakarensis.

Site-specific recombination strategies for engineering actinomycete genomes.

The feasibility of using technologies based on site-specific recombination in actinomycetes was shown several years ago. Despite their huge potential, these technologies mostly have been used for simple marker removal from a chromosome. In this paper, we present different site-specific recombination strategies for genome engineering in several actinomycetes belonging to the genera Streptomyces, Micromonospora, and Saccharothrix.

A bacterial glycosyltransferase gene toolbox: generation and applications.

The bioactivity of many natural products produced by microorganisms can be attributed to their sugar substituents. These substituents are transferred as nucleotide-activated sugars to an aglycon by glycosyltransferases. Engineering these enzymes can broaden their substrate specificity and can therefore have an impact on the bioactivity of the secondary metabolites.

Cloning and sequencing of the biosynthetic gene cluster for saquayamycin Z and galtamycin B and the elucidation of the assembly of their saccharide chains.

Sweet ways: We have investigated the glycosyltransferase genes of the saquayamycin Z (shown) and galtamycin B biosynthetic gene cluster from Micromonospora sp. Tü6368. The results unambiguously show that both compounds are derived from the same cluster.

Differences in the substrate specificity of glycosyltransferases involved in landomycins A and E biosynthesis.

A lanGT4 mutant of the landomycin A producer Streptomyces cyanogenus S136 was constructed, leading to the production of landomycin D with two deoxy sugars in the side chain and proving that LanGT4 is responsible for attaching the third deoxy sugar of the hexasaccharide side chain. Heterologous expression of lndGT4 of the landomycin E producer Streptomyces globisporus 1912 in the lanGT4 mutant restored landomycin A production, indicating that LndGT4, like LanGT4, also has the ability to work iteratively. A S.

The pig caecum model: a suitable tool to study the intestinal metabolism of flavonoids.

Pig caecum was used under anaerobic conditions to metabolize flavonoids from several classes, i.e., chrysin 1, naringenin 2, quercetin 3, and hesperetin 4.