Enhypyrazinones A and B, Pyrazinone Natural Products from a Marine-Derived Myxobacterium Enhygromyxa sp.

Abstract

To date, studies describing myxobacterial secondary metabolites have been relatively scarce in comparison to those addressing actinobacterial secondary metabolites. This realization suggests the immense potential of myxobacteria as an intriguing source of secondary metabolites with unusual structural features and a wide array of biological activities. Marine-derived myxobacteria are especially attractive due to their unique biosynthetic gene clusters, although they are more difficult to handle than terrestrial myxobacteria. Here, we report the discovery of two new pyrazinone-type molecules, enhypyrazinones A and B, from a marine-derived myxobacterium Enhygromyxa sp. Their structures were elucidated by HRESIMS and comprehensive NMR data analyses. Compounds 1 and 2, which contain a rare trisubstituted-pyrazinone core, represent a unique class of molecules from Enhygromyxa sp.

Supercritical Fluid Extraction Enhances Discovery of Secondary Metabolites from Myxobacteria

“…UAE consisted of two subsequent extraction steps, which were adapted from the most common extraction procedures conducted for myxobacterial natural products from 2018–2020 (see Chapter S3.1 Supporting Information). − ,− First, 100 mL of MeOH was added and the pellet sonicated for 1 h. After removal of MeOH, 100 mL of acetone was added, and the pellet was sonicated for another 1 h. The two extracts were combined, and the solvent was removed under reduced pressure. The residues were dissolved in 4 mL of MeOH each.…”

“…Novel secondary metabolites from myxobacteria isolated in the past years have almost exclusively been extracted with classical solvent extraction methods, using acetone as the most commonly used solvent. Besides acetone, only MeOH and ethyl acetate (EtOAc) were used. − …”

New metabolites from Streptomyces pseudovenezuelaeNA07424 and their potential activity of inducing resistance in plants against Phytophthora capsici

“…Pyrazinone derivatives are a class of natural products synthesized by non-ribosomal peptide synthases (NRPS), which are widely distributed in nature and can be produced by many microorganisms, such as actinomycetes and myxcobacteria. [20][21][22] 3,6-disubstituted pyrazione natural products, such as tyrvalin, phevalin, and leuvalin, have been reported and the biosynthesis of 3,6-disubstituted pyrazione natural products has been studied greatly, 23 in which the pyrazinone ring is constructed by two module NRPS and C-terminal reductase (R) domain. 24,25 However, the skeleton of compounds 1 and 2 containing a 3,5,6-trisubstituted pyrazione ring was rare and research on the biosynthesis of 3,5,6-trisubstituted pyrazione compounds was seldom reported, which attracted our interest.…”

2(1H)-Pyrazinones from acyclic building blocks: methods of synthesis and further derivatizations

“…[6][7][8] Other examples are sorazinone B (5) and enhypyrazinone A (6), which have been more recently isolated from myxobacteria species. 9,10 The pyrazinone skeleton is also found in the bromotyrosine alkaloids ma'edamines A and B (7a,b), isolated from an Okinawan sponge Suberea sp., 11 dragmacidin D (8), and the more elaborated dragmacidins E and F, [12][13][14] which are present in several marine sponges species like Dragmacidon, Halicortex, Spongosorites and Hexadella, as well as the peptidyl metabolite JBIR-56 (9), isolated from a marine Streptomyces. 15 Apart from constituting the central core in different natural products, the 2(1H)-pyrazinone scaffold has also been described as a key building block of great usefulness for many synthetic applications in drug design and medicinal chemistry programs, including the preparation of pharmacologically active derivatives (Fig.…”