No abstract

The genus Sorangium synthesizes approximately half of the secondary metabolites isolated from myxobacteria, including the anti-cancer metabolite epothilone. We report the complete genome sequence of the model Sorangium strain S. cellulosum So ce56, which produces several natural products and has morphological and physiological properties typical of the genus. The circular genome, comprising 13,033,779 base pairs, is the largest bacterial genome sequenced to date. No global synteny with the genome of Myxococcus xanthus is apparent, revealing an unanticipated level of divergence between these myxobacteria. A large percentage of the genome is devoted to regulation, particularly post-translational phosphorylation, which probably supports the strain's complex, social lifestyle. This regulatory network includes the highest number of eukaryotic protein kinase-like kinases discovered in any organism. Seventeen secondary metabolite loci are encoded in the genome, as well as many enzymes with potential utility in industry.Natural products and their derivatives provide the basis for medicines targeting a wide range of human diseases. The Gram-negative myxobacteria, members of the d-subgroup of proteobacteria, are an important source of novel classes of secondary metabolites 1 . Of these, the genus Sorangium is particularly valuable, as 46% of metabolites isolated from myxobacteria 1 , including the potent antitumor compound epothilone 2 , derive from this group. The majority of myxobacterial metabolites are polyketides, nonribosomal polypeptides or hybrids of the two structures, many of which are synthesized on gigantic molecular assembly lines composed of polyketide synthase (PKS) and nonribosomal polypeptide synthetase (NRPS) multienzymes 3 . Sorangium strains exhibit additional characteristic features, including 'social behavior' , cell movement by gliding, biofilm formation and morphological differentiation culminating in complex multicellular structures called fruiting bodies 4 . Three myxobacterial suborders are known 5 and the availability of the genome sequence of Myxococcus xanthus (Cystobacterineae) 6 enables comparative analysis with the Sorangium cellulosum (Sorangiineae) genome to illuminate the basis for several important behavioral and metabolic differences. These include the ability of Sorangium strains to degrade complex plant materials (Fig. 1). S. cellulosum So ce56, an obligate aerobe, was established previously as a model Sorangium strain 7 by virtue of its favorable growth characteristics and ability to differentiate reproducibly under laboratory conditions. It synthesizes the cytotoxic chivosazoles 7 and the catecholate-type siderophores myxochelins 8 . Comparison of the complete genome sequence of strain S. cellulosum

Structure elucidation of natural products including the absolute configuration is a complex task that involves different analytical methods like mass spectrometry, NMR spectroscopy, and chemical derivation, which are usually performed after the isolation of the compound of interest. Here, a combination of stable isotope labeling of Photorhabdus and Xenorhabdus strains and their transaminase mutants followed by detailed MS analysis enabled the structure elucidation of novel cyclopeptides named GameXPeptides including their absolute configuration in crude extracts without their actual isolation.

TGA2.2 is a major component of either complex, asshown by supershift analysis and Western blot analysis of DNA affinity-purified SARP. Minor amounts of a protein immunologically related to TGA2.1 were detected, whereas TGA1a was not detectable. Overexpression of either TGA2.2 or a dominant negative TGA2.2 mutant affected both SA and auxin (2,4D) inducibility of various target promoters encoding as-1-like elements, albeit to different extents. This indicates that TGA2.2 is a component of the enhancosome assembling on these target promoters, both under elevated SA and 2,4D concentrations. However, the effect of altered TGA2.2 levels on gene expression was more pronounced upon SA treatment than upon 2,4D treatment.