Chemistry and Biology of Natural Azoxy Compounds

Abstract

Azoxy compounds belong to a small yet intriguing group of natural products sharing a common functional group with the general structure RNN+(O–)­R. Their intriguing chemical structures, diverse biological activities, and important industrial applications have received attention from researchers in natural product chemistry, total synthesis, and biosynthesis. This review presents current updates about the structural diversity of natural azoxy compounds isolated from different organisms and highlights the enzymes and biological logic involved in their construction. We assume that the identification of key enzymes will provide efficient tools in biocatalysis to generate new azoxy compounds, while genome mining may result in novel natural azoxy compounds of medical and industrial interest.

High-Throughput Functional Annotation of Natural Products by Integrated Activity Profiling

“…Structure determination of the more stable isomer using a full suite of NMR and spectroscopic techniques (Supplementary Note 6, NMR spectra as Supplementary Figures 19-28) identified parkamycin A as a novel natural product containing the highly unusual biphenylazoxy core pharmacophore. While azoxy motifs have some precedent in medicinal chemistry there are very few examples of this motif in nature (46). These results demonstrate the value of ‘chemistry-first’ prioritization methods for discovering novel natural product scaffolds with biological activities not represented in the reference compound training set.…”

Amino Acid Based Antimicrobial Agents – Synthesis and Properties

“…Azoxybacillin (Figure 8) is an antifungal antibiotic produced by Bacillus cereus [143] . This is one of the very few compounds of natural origin containing the azoxy group [144] . Azoxybacilin exhibits a broad spectrum of antifungal activity in methionine‐free environments.…”

“… [143] This is one of the very few compounds of natural origin containing the azoxy group. [144] Azoxybacilin exhibits a broad spectrum of antifungal activity in methionine‐free environments. The mechanism of antifungal action of this antibiotic is connected with a fungi‐specific pathway of l ‐methionine biosynthesis, [145] particularly at the sulfur acquisition step, by influence on expression of two genes involved in regulation of sulfite reductase activity, namely MET4 and MET10.17 .…”

New azodyrecins identified by a genome mining-directed reactivity-based screening

“…Azoxy natural products are a rare yet intriguing class of natural products with various beneficial biological properties, such as antibacterial, antifungal, nematicidal, and cytotoxic activities (Figure 1) [1][2][3]. Since the discovery of the natural azoxy compound macrozamin in 1951 as the first example of a nitrogen-nitrogen bond-containing natural product [4], azoxy compounds have been isolated from various natural sources including bacteria, fungi, plants, and marine sponges [1][2][3]. Azoxy natural products have occasionally been discovered by conventional isolation schemes guided by biological activities or physicochemical properties, which are not selective for the azoxy functionality.…”