Metabolic and Biosynthetic Diversity in Marine Myxobacteria

Abstract

Prior to 2005, the vast majority of characterized myxobacteria were obtained from terrestrial habitats. Since then, several species of halotolerant and even obligate marine myxobacteria have been described. Chemical analyses of extracts from these organisms have confirmed their ability to produce secondary metabolites with unique chemical scaffolds. Indeed, new genera of marine-derived myxobacteria, particularly Enhygromyxa, have been shown to produce novel chemical scaffolds that differ from those observed in soil myxobacteria. Further studies have shown that marine sponges and terrestrial myxobacteria are capable of producing similar or even identical secondary metabolites, suggesting that myxobacterial symbionts may have been the true producers. Recent in silico analysis of the genome sequences available from six marine myxobacteria disclosed a remarkably versatile biosynthetic potential. With access to ever-advancing tools for small molecule and genetic evaluation, these studies suggest a bright future for expeditions into this yet untapped resource for secondary metabolites.

Individual Physiological Adaptations Enable Selected Bacterial Taxa To Prevail during Long-Term Incubations

“…Thus, the identification of related Spongiibacter genes in our metagenome data sets and detection of the respective proteins in our metaproteome samples indicate an active role of such bioactive peptides in these long-term cultivations. However, as the presence of secondary metabolism-related genes may vary between species within the same genus (50)(51)(52), this hypothesis will need to be evaluated in future studies.…”

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

“…Supplementary Materials: The following are available online at http://www.mdpi.com/1660-3397/17/12/698/s1, Figure S1: 1 H NMR spectrum of enhypyrazinone A (1; 600 MHz, DMSO-d 6 ), Figure S2: 13 C NMR spectrum of enhypyrazinone A (1; 125 MHz, DMSO-d 6 ), Figure S3: gCOSY spectrum of enhypyrazinone A (1; 600 MHz, DMSO-d 6 ), Figure S4: gHSQC spectrum of enhypyrazinone A (1; 600 MHz, DMSO-d 6 ), Figure S5: gHMBC spectrum of enhypyrazinone A (1; 600 MHz, DMSO-d 6 ), Figure S6: 1 H-15 N HMBC spectrum of enhypyrazinone A (1; 600 MHz, DMSO-d 6 ), Figure S7: Positive ion HRESIMS of enhypyrazinone A (1), Figure S8: 1 H NMR spectrum of enhypyrazinone B (2; 500 MHz, CDCl 3 /CD 3 OD 1:1), Figure S9: 13 C NMR spectrum of enhypyrazinone B (2; 125 MHz, CDCl 3 /CD 3 OD 1:1), Figure S10: gCOSY spectrum of enhypyrazinone B (2; 500 MHz, CDCl 3 /CD 3 OD 1:1), Figure S11: gHSQC spectrum of enhypyrazinone B (2; 500 MHz, CDCl 3 /CD 3 OD 1:1), Figure S12: gHMBC spectrum of enhypyrazinone B (2; 500 MHz, CDCl 3 /CD 3 OD 1:1), Figure S13: 1 H-15 N HMBC spectrum of enhypyrazinone B (2; 500 MHz, CDCl 3 /CD 3 OD 1:1), Figure S14: 1 H NMR spectrum of enhypyrazinone B (2; 500 MHz, DMSO-d 6 ), Figure S15: 13 C NMR spectrum of enhypyrazinone B (2; 125 MHz, DMSO-d 6 ), Figure S16: gCOSY spectrum of enhypyrazinone B (2; 500 MHz, DMSO-d 6 ), Figure S17: gHSQC spectrum of enhypyrazinone B (2; 500 MHz, DMSO-d 6 ), Figure S18: gHMBC spectrum of enhypyrazinone B (2; 500 MHz, DMSO-d 6 ), Figure S19: 1 H- 15 N HMBC spectrum of enhypyrazinone B (2; 500 MHz, DMSO-d 6 ), Figure S20: Positive ion HRESIMS of enhypyrazinone B (2), Table S1: 1 H and 13 C NMR data for enhypyrazinone B (2) (500 MHz for 1 H, 125 MHz for 13 C, CDCl 3 /CD 3 OD 1:1).…”

“…Recently, however, four new genera of halotolerant and obligate marine myxobacteria, Enhygromyxa, Haliangium, Plesiocystis, and Pseudenhygromyxa, have been discovered and classified [4][5][6][7][8][9]. Although not extensively studied, the limited records of marine-derived myxobacteria indicate their immense potential as prolific producers of novel natural compounds with prominent biological activities, making these social microbes highly attractive for drug discovery [10][11][12][13][14][15][16]. The genus Enhygromyxa, in particular, has been shown to produce novel bioactive molecules, including salimabromide [17], salimyxins A and B [18], enhygrolides A and B [18], enhygromic acid [19], and deoxyenhygrolides A and B ( Figure 1) [19].…”

Future Directions of Marine Myxobacterial Natural Product Discovery Inferred from Metagenomics

“…Marine-derived myxobacteria have already demonstrated a strong potential to produce natural products with distinct scaffolds [ 36 , 37 , 38 , 39 , 40 , 41 ]. Many of these materials display unique structure features as exemplified by the enhygrolides [ 36 ], enhygromic acid [ 37 ], haliamide [ 38 ], haliangicin [ 39 , 40 ], miuraenamide [ 15 , 16 ], salimabromide [ 41 ], and the salimyxins [ 36 ] (the structures of these materials are provided in the accompaning manuscript [ 10 ]). Many of these materials have demonstrated potent biological activity [ 42 ].…”

“…It took until 1998 that the first truly obligate halophilic and halotolerant groups were reported [ 4 , 5 , 6 , 7 , 8 , 9 ]. Interest in these species has arisen due to their profound ability to produce secondary metabolites that can serve as leads for drug discovery efforts [ 10 ]. Myxobacteria have since been shown to inhabit the marine and estuarine environments often found in sediments or on seagrass and algae [ 4 , 5 , 6 , 7 , 8 ].…”