Homospermidine Lipids: A Compound Class Specifically Formed during Fruiting Body Formation of Myxococcus xanthus...

The fascinating ability of myxobacteria to form multicellular spore filled fruiting bodies under starvation conditions was widely studied as a model for cooperative microbial behavior. The potential of a life cycle induced change of secondary metabolism, as a means to discover novel natural products, remains largely underexplored. We therefore studied the model organism Myxococcus xanthus DK1622 under submersed and solid cultivation conditions to find putatively life-cycle related compounds by applying statistical analysis on analytical data. Utilizing the advantageous characteristics of LC-MS, LC-MS/MS, and MALDI-MSI allowed the identification of compounds unambiguously associated with myxobacterial fruiting bodies. Our screening effort resulted in the purification and structure elucidation of a novel compound, the homospermidine lipid, from cultures that had undergone the fruiting process. A combination of molecular networking and targeted LC-MS/MS in conjunction with our in-house metabolomics database subsequently revealed alternative producers of the respective compound as well as a number of compounds belonging to the same structural class. Three further members of this compound class were isolated from an alternative producer and structurally elucidated by NMR. Insights into the biosynthesis of this novel compound class was gained by feeding of isotopically labeled substrates and in silico analysis.