Discovery, Biosynthesis and Biological Activity of a Succinylated Myxochelin from the Myxobacterial Strain MSr12020

Abstract

Myxobacteria feature unique biological characteristics, including their capability to glide on the surface, undergo different multicellular developmental stages and produce structurally unique natural products such as the catecholate-type siderophores myxochelins A and B. Herein, we report the isolation, structure elucidation and a proposed biosynthesis of the new congener myxochelin B-succinate from the terrestrial myxobacterial strain MSr12020, featuring a succinyl decoration at its primary amine group. Myxochelin-B-succinate exhibited antibacterial growth inhibition and moderate cytotoxic activity against selected human cancer cell lines. This unique chemical modification of myxochelin B might provide interesting insights for future microbiological studies to understand the biological function and biosynthesis of secondary metabolite succinylation.

Recent advances in discovery and biosynthesis of natural products from myxobacteria: an overview from 2017 to 2023

“…Hitherto, siderophores from myxobacteria could be mainly categorized into three subfamilies, namely, the catecholate-type such as the myxochelins 160 and hyalachelins, 161 the citrate-hydroxamate-type such as the nannochelins, 162 and the more recently discovered sorangibactins. 81 Myxochelins are the best-studied siderophores in the myxobacterial realm, [163][164][165][166][167][168][169] which are widely distributed in different genera such as Myxococcus, Corallococcus, Archangium, 81 Sorangibactins feature a linear polycyclic architecture consisting of an N-terminal ortho-phenol, an oxazole, two N-methyl-thiazolidines, and an unusual C-terminal homocysteine (thiolactone) moiety that is probably incorporated by an unusual thioesterase (TE) domain in a non-canonical NRPS assembly line. The homocysteine group in 191 and 192 is prone to ring-opening under an acidic condition, resulting in the production of 193.…”

Structure Elucidation and Biosynthesis of Nannosterols A and B, Myxobacterial Sterols from Nannocystis sp. MNa10993

“…11 The chosen parameters to evaluate those MS data sets considering the exact mass (exact mass deviation below 5 ppm), isotope pattern, and retention time matching (retention time deviation below 0.3 min) were adapted from previous studies investigating the presence of different myxochelin congeners. 47,48 Isolation of 1 and 2 by Semipreparative HPLC. The extraction, isolation, and purification of 1 and 2 from the myxobacterial broth was initiated by liquid−liquid extraction to concentrate the nannosterols in the chloroform (CHCl 3 ) and ethyl acetate (EA) phase.…”

“…The in-house standard extract database embedded in the software bundle Mxbase Explorer 3.2.27 was used for the search of alternative producers of 1 and 2 . The chosen parameters to evaluate those MS data sets considering the exact mass (exact mass deviation below 5 ppm), isotope pattern, and retention time matching (retention time deviation below 0.3 min) were adapted from previous studies investigating the presence of different myxochelin congeners. , …”

“… 11 The chosen parameters to evaluate those MS data sets considering the exact mass (exact mass deviation below 5 ppm), isotope pattern, and retention time matching (retention time deviation below 0.3 min) were adapted from previous studies investigating the presence of different myxochelin congeners. 47 , 48 …”

Chromosomal organization of biosynthetic gene clusters suggests plasticity of myxobacterial specialized metabolism including descriptions for nine novel species:Archangium lansiniumsp. nov.,Myxococcus landrumussp. nov.,Nannocystis bainbridgeasp. nov.,Nannocystis poenicansasp. nov.,Nannocystis radixulmasp. nov.,Polyangium mundeleiniumsp. nov.,Pyxidicoccus parkwaysissp. nov.,Sorangium ateriumsp. nov.,Stigmatella ashevillenasp. nov

“…Although limited to metabolic profiles of axenically grown myxobacteria, this observation suggests investigation of lesser-studied genera within the phylum Myxococcota might increase the likelihood of metabolite discovery. Ongoing natural product discoveries from novel species of myxobacteria reinforce the need for continued isolation and characterization of environmental myxobacteria (6)(7)(8)(9). Most recently described Myxococcota belong to the genera Corallococcus, Myxococcus, and Pyxidicoccus (10)(11)(12)(13)(14), and comparatively fewer members of lesser-studied myxobacterial taxa have been reported over the last decade (15)(16)(17).…”