From Ocean to Medicine: Pharmaceutical Applications of Metabolites from Marine Bacteria

Abstract

Oceans cover seventy percent of the planet's surface and besides being an immense reservoir of biological life, they serve as vital sources for human sustenance, tourism, transport and commerce. Yet, it is estimated by the National Oceanic and Atmospheric Administration (NOAA) that eighty percent of the oceans remain unexplored. The untapped biological resources present in oceans may be fundamental in solving several of the world's public health crises of the 21st century, which span from the rise of antibiotic resistance in bacteria, pathogenic fungi and parasites, to the rise of cancer incidence and viral infection outbreaks. In this review, health risks as well as how marine bacterial derived natural products may be tools to fight them will be discussed. Moreover, an overview will be made of the research pipeline of novel molecules, from identification of bioactive bacterial crude extracts to the isolation and chemical characterization of the molecules within the framework of the One Health approach. This review highlights information that has been published since 2014, showing the current relevance of marine bacteria for the discovery of novel natural products.

Keywords: One Health; anticancer; antimicrobial resistance; antimicrobials; antivirals; bioactive marine bacteria; cancer incidence; drug discovery; marine natural products.

Figure 1

Bioactive metabolites isolated from marine organisms. Halichondrin B (1), a macrolide first isolated from H. okadai but also present in other sponges. Bryostatin 1 (2), which belongs to a family of polyketide macrolides first identified in the marine bryozoan B. neritina. Salinosporamide A (3), is a proteasome inhibitor isolated from bacteria from the genus Salinospora and is in phase III clinical trials for the treatment of multiple myeloma.

Figure 2

Examples of recently isolated antimicrobial natural products from marine bacteria. Bacicyclin (4), a cyclic peptide isolated from a Bacillus sp. BC028. Anthramicin B (5), a polyketide isolated from S. cyaneofuscatus M-169. Taromycin B (6), a lipopeptide from Saccharomonospora sp. CNQ-490. Janthinopolyenemycin A (7) and Janthinopolyenemycin B (8). The janthinopolyenemycins are polyketides isolated from two strains of the genus Janthinobacterium. Streptoseomycin (9), a macrolactone isolated from S. seoulensis. Ansalactam B (10), a pentacyclic polyketide. Ansalactam C (11), an open polyketide unlike ansalactam B. Ansalactam D (12), a hexacyclic polyketide. Ansalactams B, C and D were isolated from Streptomyces sp. CNH189. Micromonohalimane A (13). Micromonohalimane B (14). Micromonohalimanes A and B are terpenes isolated from Micromonospora sp. WMMC-218. Xestostreptin (15), a diketopiperazine isolated from Streptomyces sp. S.4. Branimycin B (16) and Branimycin C (17) C are macrolides isolated from the deep-sea bacterium P. carboxydivorans M-227. Lobosamide A (18), Lobosamide B (19) and Lobosamide C (20) are macrolactams isolated from Micromonospora sp. RL09-050-HVF-A. Salinipostin A (21), a bicyclic phosphotriester isolated from Salinispora sp. RLUS08-036-SPS-B.

Figure 3

Examples of recently isolated antimicrobial natural products from marine bacteria. Mollemycin A (22) is a hybrid peptide-polyketide isolated from Streptomyces sp. CMB-M0244. Actinosporin A (23), a polyketide isolated from Actinokineospora sp. EG49. Gageopeptide A (24). Gageopeptide B (25). Gageopeptide C (26), Gageopeptide D (27), Gageotetrin A (28). Gageotetrin B (29). Gageotetrin C (30). Gageostatin A (31). Gageostatin B (32). Gageostatin C (33). The gageopeptides, gageotetrins and gageostatins are linear lipopeptides isolated from B. subtilis 109GGC020.

Figure 4

Examples of recently isolated natural products from marine bacteria with antiviral activity. Neoabyssomicin D (34). Neoabyssomicin F (35) and Neoabyssomicin E (36) are polycyclic polyketides isolated from S. koyangensis SCSIO 5802. Wailupemycin J (37) and (R)-wailupemycin K (38) are phenolic polyketides isolated from Streptomyces sp. OUCMDZ-3434. Xiamycin C (39), Xiamycin D (40) and Xiamycin E (41) were isolated from Streptomyces sp. #HK18.

Figure 5

Examples of recently isolated cytotoxic natural products from marine bacteria. Dentigerumycin E (42), a cyclic hexapeptide isolated from S. albogriseolus JB5. Neothioviridamide (43), a cyclic peptide from Streptomyces sp. MSB090213SC12. Rakicidin G (44), Rakicidin H (45) and Rakicidin I (46) are cyclic depsipeptides isolated from M. chalcea FIM 02–523. FW05328-1 (47), a polyene macrolactam isolated from Micromonospora sp FIM05328. Neaumycin B (48), a macrolide from Micromonospora sp. CNY-010. Pactamide A (49), a polyketide isolated from S. pactum SCSIO 02999. Streptodepsipeptide P11A (50) and Streptodepsipeptide P11B (51) are cyclodepsipeptides from Streptomyces sp. P11-23B. Antimycin E (52), Antimycin F (53), Antimycin G (54) and Antimycin H (55) are alkaloids isolated from Streptomyces sp. THS-55. Piericidin F (56) is an alkaloid isolated Streptomyces sp. CHQ-64.

Figure 6

Examples of recently isolated cytotoxic natural products from marine bacteria. Neo-actinomycin A (57) and Neo-actinomycin B (58) are chromopeptides from Streptomyces sp. IMB094. PM100117 (59) and PM100118 (60) are macrolides isolated from S. caniferus GUA-06-05-006A. Lobophorin I (61), a spirotetronate isolated from Streptomyces sp. 1053U.I.1a.3b. Haliamide (62), a hybrid of a polyketide synthase from H. ochraceum SMP-2. Tetra(indol-3-yl)ethenone (63), an indole isolated from P. denitrificans BBCC725. O-Demethylpederin (64), a polyketide with a tetrahydropyran-core from Labrenzia sp. PHM005.

Figure 7

Examples of recently isolated bacterial natural products employing the GNPS and SMART technologies. Lugdunomycin (65), a novel angucycline-derived polycyclic aromatic polyketide with antimicrobial properties, isolated from Streptomyces sp. QL37 utilising a metabolomic combined with MS-based molecular networking analysis. Accramycin A (66), a naphthacene-type aromatic polyketide isolated from Streptomyces sp. MA37, which characterization was aided by MS/MS molecular networking. Noursamycin A (67), Noursamycin B (68), Noursamycin C1 (69), Noursamycin C2 (70), Noursamycin D (71) and Noursamycin E (72) are chlorinated cyclic hexapeptides isolated from S. noursei with the aid of MS/MS molecular networking. Symplocolide A (73), a swinholide-like macrolide with cytotoxic properties obtained from extracts of the filamentous marine cyanobacterium Symploca sp. by employing both SMART technologies and MS/MS molecular networking.