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Updated: Feb 1, 2026

Mass Spectrometry-Guided Genome Mining as a Tool to Uncover Novel Natural Products
Published on: March 12, 2020
Novel Methoxymethacrylate Natural Products Uncovered by Statistics-Based Mining of the Myxococcus fulvus Secondary
Fabian Panter1,2, Daniel Krug1,2, Rolf Müller1,2
1Department of Microbial Natural Products, Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI) and Department of Pharmacy , Saarland University , Campus E8 1 , 66123 Saarbrücken , Germany.
Abstract:
This study reports the uncovering of new myxobacterial natural products through comprehensive analysis of the Myxococcus fulvus secondary metabolome. Statistics-based mining of mass spectrometry data paved the way for full structure elucidation of two new secondary metabolites named fulvuthiacene A and B, and investigation of the underlying biosynthetic pathway revealed an evolutionary link between the fulvuthiacene hybrid polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) gene cluster and the related myxothiazol and melithiazol assembly lines. Detailed characterization of the post-PKS modification enzyme cascade responsible for the fulvuthiacenes' terminal β-methoxy-methyl acrylate moiety was pursued by heterologous expression of these enzymes in the myxothiazol producer Stigmatella aurantiaca DW4/3-1. The discovery of fulvuthiacenes provides new insights into the overall structure-activity relationship picture for the β-methoxyacrylate class of respiratory chain inhibitors and might thus serve as starting point for the development of next-generation β-methoxymethacrylate fungicides.
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