Abstract
ABSTRACTGenomic information from various magnetotactic bacteria suggested that besides their common ability to form magnetosomes, they potentially also represent a source of bioactive natural products. By using targeted deletion and transcriptional activation, we connected a large biosynthetic gene cluster (BGC) of the trans-acyltransferase polyketide synthase (trans-AT PKS) type to the biosynthesis of a novel polyketide in the alphaproteobacterium Magnetospirillum gryphiswaldense. Structure elucidation by mass spectrometry and nuclear magnetic resonance spectroscopy (NMR) revealed that this secondary metabolite resembles sesbanimides, which were very recently reported from other taxa. However, sesbanimide R exhibits an additional arginine moiety the presence of which reconciles inconsistencies in the previously proposed sesbanimide biosynthesis pathway observed when comparing the chemical structure and the potential biochemistry encoded in the BGC. In contrast to the case with sesbanimides D, E, and F, we were able to assign the stereocenter of the arginine moiety experimentally and two of the remaining three stereocenters by predictive biosynthetic tools. Sesbanimide R displayed strong cytotoxic activity against several carcinoma cell lines.
Highlights
Genomic information from various magnetotactic bacteria suggested that besides their common ability to form magnetosomes, they potentially represent a source of bioactive natural products
We unambiguously assigned a new member of the sesbanimide compound family to a trans-AT polyketide synthase biosynthetic gene cluster from Magnetospirillum gryphiswaldense by inactivation and overexpression of the cluster and statistical analysis of the strains’ metabolome
Sesbanimide R belongs to the sesbanimide family of natural products
Summary
Genomic information from various magnetotactic bacteria suggested that besides their common ability to form magnetosomes, they potentially represent a source of bioactive natural products. Studies on MTB so far have focused mainly on understanding magnetosome structure, biosynthesis, and biological function as well as exploring the potential utility of magnetosomes as magnetic nanoparticles for various applications, such as magnetic imaging or magnetic hyperthermia, magnetosome-based immunoassays, and as nanocarriers in magnetic drug targeting and multifunctional nanomaterials with versatile functional moieties [2,3,4,5,6,7] Apart from their common ability to form magnetosomes, MTB represent a highly heterogeneous group of prokaryotes. Araujo et al [22] first noted the presence of typical secondary metabolite biosynthetic gene clusters (BGCs), such as putative polyketide synthases (PKSs) and nonribosomal peptide synthetases (NRPSs), in the genomes of several MTB This so far has remained an untapped source for discoveries, largely owing to the fact that most of these bacteria are not tractable; many cannot be cultured in the laboratory
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