Seaweed symbionts reveal treasure trove of potential drug compounds

By Dr. Sanchari Sinha Dutta, Ph.D.Nov 1 2023Reviewed by Benedette Cuffari, M.Sc.

In a recent study published in Marine Drugs, scientists review natural bioactive compounds produced by marine macroalgae-related Bacillota and their pharmacological properties. 

Study: Natural Products and Pharmacological Properties of Symbiotic Bacillota (Firmicutes) of Marine Macroalgae. Image Credit: Created with the assistance of DALL·E 3

Background

Marine macroalgae serve as a rich source of novel bioactive compounds with potential pharmacological properties. However, unlike bioactive compounds produced by terrestrial microorganisms, few studies have assessed the chemical and biological properties of marine microorganisms.

Marine macroalgae or seaweeds host a wide range of bacterial species. The association between host algae and symbionts, such as bacteria or other microorganisms, depends on the type of nutrients provided by the host. Bacterial symbionts also facilitate their host by producing essential metabolites, as well as antimicrobial and antifouling agents, that protect the host from harmful organisms and substances.

Bacillota has been identified as the bacterial phylum most commonly associated with marine macroalgae. Moreover, Bacillota typically comprises Gram-positive bacteria.

Bacillota utilize over 9% of their genome to encode biosynthetic gene clusters and produce novel bioactive compounds belonging to different chemical classes, including terpenes, polyketides, non-ribosomal peptides, lasso peptides, bacteriocins, thiopeptides, ectoine, and melanin.    

Metabolites produced by bioactive Bacillota

Marine macroalgae serve as a rich source of bioactive Bacillota. Culturing marine macroalgae-related Bacillota in laboratory settings has led to the production of several bioactive compounds, most of which are polyketides.

Macrolides are polyketide macrocyclic lactones of varying ring sizes. These highly oxygenated polyenes exhibit a broad spectrum of antibacterial effects against pathogenic bacteria.

A total of 25 macrolides have been identified from marine macroalgae-related Bacillota, including derivatives of macrolactin, bacvalactone, elansolid, difficidin, and macrobrevin. In addition to their antibacterial properties, these macrolides are known to have anticancer, antidiabetic, anti-inflammatory, and neuroprotective properties.

Different novel derivatives of heterocyclic and aliphatic esters have been isolated from macroalgae Bacillota. Some compounds isolated from B. subtilis of Sargassum myriocystum include pyranyl benzoate analogs, which are synthesized by the Claisen condensation, dehydration, and ketoreduction pathways.

B. amyloliquefaciens isolated from Padina gymnospora, a brown algae, produces polyketides through the polyketide synthase-1 gene cluster. Other polyketide synthase-1 gene products include heterocyclic esters that are secondary metabolites of red algae-isolated B. amyloliquefaciens.      

Furanoterpenoids (terpenoids) isolated from macroalgae Bacillota (B. subtilis of red alga) exhibit antimicrobial and anti-inflammatory properties. However, these compounds are known to cause toxicity in humans by producing reactive electrophilic intermediates that can bind to and damage cellular macromolecules. 

Amicoumacins are the derivatives of dihydroisocoumarins that are produced through bacterial non-ribosomal peptides synthetase gene clusters. These compounds are known to have antibacterial, anti-ulcer, anti-inflammatory, and cytotoxic properties.

Pharmacological properties of macroalgae Bacillota-derived metabolites

Bacillus species are the most common type of marine Bacillota related to macroalgae. These species utilize over 7% of their genome to produce bioactive compounds with antimicrobial properties.

Compounds isolated from macroalgae Bacillota exhibit strong antimicrobial effects against pathogenic bacteria that infect humans. Difficidin analogs isolated from red alga-related B. amyloliquefaciens exhibit the highest antimicrobial effects against a broad spectrum of pathogenic bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis.

Likewise, the compounds isolated from B. velezensis of Laurencia papillosa (red alga) exhibit antimicrobial effects against MRSA and Vibrio haemolyticus. Each of these compounds exhibits antimicrobial effects at micromolar concentrations.  

In addition to their antimicrobial properties, anti-inflammatory, antioxidant, antidiabetic, anti-hypercholesterolemic, anti-hyperglycemic, and cytotoxic properties of macroalgae Bacillota extracts and fractions have been widely studied.

In vitro studies have reported the antifungal activity of a volatile fraction of B. amyloliquefaciens isolated from Zonaria tournefortii. Similarly, an acetone extract of a Bacillus species isolated from a brown alga has been found to exert cytotoxic effects against colon cancer cells.

Significance

Marine macroalgae-related Bacillota is a rich source of novel bioactive compounds with various pharmacological properties. To date, only a small fraction of the verse marine macroalgae populations have been studied through in vitro and in silico antibacterial bioassays for chemical constituents of their Bacillota.

However, for the discovery of novel therapeutic agents from macroalgae Bacillota, in vivo studies using different animal models are needed to assess the safety, bioavailability, and therapeutic efficacy of Bacillota-derived compounds. More diverse bioassays are also needed to expand the bioactivity profiles of these novel compounds beyond their well-known antibacterial properties.