Table 3.

The potential functions of the array of specialized metabolites encoded by Red Sea brine SMGCs. SMGCs are named as denoted by antiSMASH tool [45]. Hyphens indicate hybrid clusters. Cf_fatty_acid: fatty acid putative cluster. Cf_putative: unknown type putative cluster. Cf_saccharide: saccharide putative cluster. Hserlactone: cluster coding for homoserine lactone. Lantipeptide: cluster coding for lanthipeptide. NRPS: cluster coding for non-ribosomal peptide synthetase. OtherKS: cluster coding for other types of polyketide synthases. Pufa: cluster coding for poly-unsaturated fatty acids. T1pks: type I polyketide synthase. T2pks: type II polyketide synthase. T3pks: type III polyketide synthase.

General Functional Classification:	Product (Enzyme)		Gene Cluster Names	Representative Basic Structure	Potential Function/Application of Product	Percentage of Total SMGCs
1. Products of predicted functions commonly abundant in microbes	Saccharide		Cf_saccharide Cf_saccharide-Bacteriocin Cf_saccharide-nrps Cf_fatty_acid-Cf_saccharide T3pks-cf_saccharide	-	Microbe-host interactions e.g. lipopolysaccharides. Some saccharides that are diffusible were reported to have antibacterial activities [46,47].	80.61%
	Fatty Acid		Cf_fatty_acid Arylpolyene-cf_fatty_acid Cf_fatty_acid-Arylpolyene Cf_fatty_acid-Cf_saccharide Ladderane-Cf_fatty_acid T2pks-Cf_fatty_acid	-	Structural functions and reported that composition can change as an adaptation to temperature and pressure in the environment [48].	7.69%
	Aryl polyenes		Arylpolyene Arylpolyene-cf_fatty_acid Cf_fatty_acid-Arylpolyene		Aryl polyene SMGCs found in abundance in Gram negative bacteria. Previously reported to have a protective role from damage caused by reactive oxygen species [46,49].	0.52%
	Acyl-homoserine lactones		Hserlactone		Quorum sensing [50].	0.03%
2. Subset of products with potential antibacterial and/or anticancer effects:	Terpenes		Terpene		A subset of the terpenes possesses antibacterial effect [51].	1.89%
	Peptides	Ribosomal peptides	Bacteriocin Cf_saccharide-Bacteriocin Microcin Lantipeptide		Some have antibacterial activity, and some have selective cancer cytotoxic activity [52].	0.78%
		Non-ribosomal peptides	Cf_saccharide-nrps NRPS Nrps-T1pks	-	Many non-ribosomal peptides have antibacterial (e.g., β-lactams) and anticancer (e.g. bleomycin) effects [53].	0.25%
	Polyketides	(Type I Polyketide synthase)	Nrps-T1pks Otherks-Pufa-T1pks Otherks-T1pks T1PKS	-	A subset are responsible for antibiotic synthesis e.g. the type I polyketide synthase (PKSI) producing erythromycin [54].	0.2%
		(Type II Polyketide synthase)	T2pks-Cf_fatty_acid	-	Some type II polyketide synthase (PKSII) enzymes produce aromatic polyketide antibiotics e.g. oxytetracycline [54].	0.09%
		(Type III Polyketide synthase)	T3pks T3pks-cf_saccharide	-	Type III Polyketide synthase (PKSIII) enzymes are capable of producing an array of compounds including pyrones—a subset of pyrones were previously reported to have antibacterial and anticancer effects [55].	0.31%
	Phosphonates		Phosphonate		Some natural phosphonates are antibacterials e.g. fosfomycin. Also have structural functions [56].	0.01%
3. Miscellaneous: products are predicted to confer adaptation to the environment/special structure/unknown function:	Others		Cf_putative Other OtherKS Otherks-Pufa Otherks-Pufa-T1pks Otherks-T1pks	-	Some code for biosynthetic gene clusters of types that are still unknown [9].	8.13%
	Polyunsaturated fatty acids		Otherks-Pufa Otherks-Pufa-T1pks		Polyunsaturated fatty acids (PUFAs) are membrane adaptations to piezophiles, thermophiles and psychrophiles to prevent membrane crystallization [57,58].	0.14%
	Ectoine		Ectoine		Halophilic adaptation & effective in vitro in preventing protein misfolding characteristic in diseases e.g. Alzheimer’s [59].	0.08%
	Ladderane		Ladderane-Cf_fatty_acid		Unique component of anammoxosome membrane in anammox (anaerobic ammonium oxidizing) bacteria and potential biofuel [60].	0.05%