The secondary metabolome of marine-derived microorganisms

The focus of the current studies is on unusual, hitherto not at all researched bacterial taxa and on marine-derived fungi as a source of novel bioactive metabolites. Amongst myxobacteria [1] obligate marine strains have to date hardly been studied. We were successful in isolating such marine myxobacteria, i.e. Enhygromyxa salina strains, which are closely related to microorganisms to date termed as “unculturable”. Phylogenetic analysis and first draft genome data from E. salina strain SWB007, led us to conclude that marine myxobacteria are phylogenetically quite distinct from their terrestrial counterparts. This is also mirrored in their biosynthetic abilities. Indeed, large scale cultivation made it possible to isolate the first secondary metabolites from these bacteria, one of them being salimabromide with a novel carbon skeleton and a core structure with no resemblance to any known natural or synthetic compound [2]. Nannocystis exedens is a halotolerant myxobacterial strain that produces a new group of natural products, named phenylnannolones. Phenylnannolone A shows inhibitory activity towards the ABCB1 gene product p-glycoprotein and reverses daunorubicin resistance in cultured cancer cells. Investigations on the biosynthesis revealed a polyketide synthase (PKS) gene cluster, whose domain order is co-linear to the structure of the metabolite [3]. The ascomycete Dichotomomyces cejpii was isolated from the marine sponge Callyspongia sp. cf. C. flammea. We obtained the novel compounds dichotoindole and methoxyasporiyzin from this fungus, which are composed of an indole ring and a diterpenoid moiety, as well as the known indoloditerpenes emindole SB and JBIR-03. In ligand binding assays, JBIR-03 and methoxyasporyzin were shown to possess affinity toward CB1 and CB2 receptors. In contrast, emindole SB and the new indoloditerpene dichotoindole were identified as cannabinoid receptor antagonist preferencing CB2. Dichotoindole may thus be useful as a selectively acting pharmacological tool and/or lead for the development of potent and selective cannabinoid receptor antagonists [4].

References:

[1] T. F. Schäberle, F. Lohr, A. Schmitz, G. M. König. Nat. Prod. Rep., 2014, 31, 953.

[2] S. Felder, S. Dreisigacker, S. Kehraus, E. Neu, G. Bierbaum, P. R. Wright, D. Menche, T. F. Schäberle, G. M. König, Chem. Eur. J., 2013, 19, 9319.

[3] S. M Bouhired, M. Crüsemann, C. Almeida, T. Weber, J. Piel, T. F. Schäberle, G. M. König. ChemBioChem, 2014, 15, 757.

[4] H. Harms, V. Rempel, S. Kehraus, M. Kaiser, P. Hufendiek, C. E. Müller, G. M. König, J. Nat. Prod., 2014, 77, 673.