An investigation of secondary metabolite production stimulus in Myxobacterium
Microbial natural products are diverse molecules that perform many biologically important tasks. Many products are thought to provide a survival advantage by limiting competitor growth; additionally, over 80% of current anti-infective agents are based on natural product scaffolds. Nevertheless, new natural products are urgently needed due to the emergence of diseases such as multi-drug resistant bacteria. Genomic sequencing of select microorganisms has revealed multiple biosynthetic gene clusters capable of synthesizing diverse natural products. However, under standard laboratory conditions most encoded natural products are not synthesized and are thus unknown and considered unknown. Understanding ways to activate these biosynthetic gene clusters is a promising approach to isolate novel natural products. The primary goal of our study is to identify conditions that stimulate the production of natural products in underexplored genera of microorganisms.
Myxobacteria is one such underexplored genus. With over 40 new products discovered in the last 8 years and some products entering trials for therapeutic use, they serve as a potential reservoir for new products. We use the model myxobacterium Myxococcus xanthus DK1622. DK1622 encodes 23 biosynthetic gene clusters but only 13 have known products. Previous studies in non-myxobacteria found that sub-lethal antibiotics or rare earth metals stimulate natural product synthesis. Here, we address how these stimuli affect natural product production in DK1622. We isolate natural products in the presence and absence of putative stimuli using liquid chromatography-mass spectrometry (LC-MS) and comparative metabolomics methodologies. The study serves as a basis for understanding how stimuli affect natural product production in mxyobacteria.