Analysis of the Genome and Metabolome of Marine Myxobacteria Reveals High Potential for Biosynthesis of Novel Specialized Metabolites.

Comparative genomic/metabolomic analysis is a powerful tool to disclose the potential of microbes for the biosynthesis of novel specialized metabolites. In the group of marine myxobacteria only a limited number of isolated species and sequenced genomes is so far available. However, the few compounds isolated thereof so far show interesting bioactivities and even novel chemical scaffolds; thereby indicating a huge potential for natural product discovery. In this study, all marine myxobacteria with accessible genome data (n = 5), including Haliangium ochraceum DSM 14365, Plesiocystis pacifica DSM 14875, Enhygromyxa salina DSM 15201 and the two newly sequenced species Enhygromyxa salina SWB005 and SWB007, were analyzed. All of these accessible genomes are large (~10 Mb), with a relatively small core genome and many unique coding sequences in each strain. Genome analysis revealed a high variety of biosynthetic gene clusters (BGCs) between the strains and several resistance models and essential core genes indicated the potential to biosynthesize antimicrobial molecules. Polyketides (PKs) and terpenes represented the majority of predicted specialized metabolite BGCs and contributed to the highest share between the strains. BGCs coding for non-ribosomal peptides (NRPs), PK/NRP hybrids and ribosomally synthesized and post-translationally modified peptides (RiPPs) were mostly strain specific. These results were in line with the metabolomic analysis, which revealed a high diversity of the chemical features between the strains. Only 6-11% of the metabolome was shared between all the investigated strains, which correlates to the small core genome of these bacteria (13-16% of each genome). In addition, the compound enhygrolide A, known from E. salina SWB005, was detected for the first time and structurally elucidated from Enhygromyxa salina SWB006. The here acquired data corroborate that these microorganisms represent a most promising source for the detection of novel specialized metabolites.

Cyclopropane-Containing Fatty Acids from the Marine Bacterium Labrenzia sp. 011 with Antimicrobial and GPR84 Activity.

Bacteria of the family Rhodobacteraceae are widespread in marine environments and known to colonize surfaces, such as those of e.g., oysters and shells. The marine bacterium Labrenzia sp. 011 is here investigated and it was found to produce two cyclopropane-containing medium-chain fatty acids (1, 2), which inhibit the growth of a range of bacteria and fungi, most effectively that of a causative agent of Roseovarius oyster disease (ROD), Pseudoroseovarius crassostreae DSM 16950. Additionally, compound 2 acts as a potent partial, ß-arrestin-biased agonist at the medium-chain fatty acid-activated orphan G-protein coupled receptor GPR84, which is highly expressed on immune cells. The genome of Labrenzia sp. 011 was sequenced and bioinformatically compared with those of other Labrenzia spp. This analysis revealed several cyclopropane fatty acid synthases (CFAS) conserved in all Labrenzia strains analyzed and a putative gene cluster encoding for two distinct CFASs is proposed as the biosynthetic origin of 1 and 2.

Marine-derived myxobacteria of the suborder Nannocystineae: An underexplored source of structurally intriguing and biologically active metabolites.

Myxobacteria are famous for their ability to produce most intriguing secondary metabolites. Till recently, only terrestrial myxobacteria were in the focus of research. In this review, however, we discuss marine-derived myxobacteria, which are particularly interesting due to their relatively recent discovery and due to the fact that their very existence was called into question. The to-date-explored members of these halophilic or halotolerant myxobacteria are all grouped into the suborder Nannocystineae. Few of them were chemically investigated revealing around 11 structural types belonging to the polyketide, non-ribosomal peptide, hybrids thereof or terpenoid class of secondary metabolites. A most unusual structural type is represented by salimabromide from Enhygromyxa salina. In silico analyses were carried out on the available genome sequences of four bacterial members of the Nannocystineae, revealing the biosynthetic potential of these bacteria.

Protective effect ofAgave salmiana fructans in azoxymethane- induced colon cancer in Wistar rats.

Colon cancer is a world concerning disease; it shows a high mortality rate and may be related to eating habits. Studies using inulin-like fructans, which are produced as energy supplies by several plants, have demonstrated a chemo-protective effect of these fructans in colon cancer. However, agavins a structurally different type of fructans from the Agave genus with demonstrated prebiotic effects, have been poorly studied for their possible protective effects in cancer. The aim of the present study was to evaluate the effect ofAgave fructan-rich diets in colon cancer progress using a rat model and "Agave mezcalero potosino" A. salmiana Otto ex Salm Dick, which is widely distributed in Mexico. Results showed a significant decrease (p<0.05) in early lesions of colon cancer (aberrant crypt foci) compared with the control group. These data suggest that fructans from A. salmiana may contribute to a reduction in the risk of colon cancer as well as inulin-like compounds.