Exploring the bioactive landscape: peptides and non-peptides from the human microbiota

Abstract

The human microbiota, consisting of trillions of bacteria from six main phyla, produces peptide and non-peptide secondary metabolites which have antibacterial properties vital to medicine and biotechnology. These metabolites influence biological processes linked to diseases, yet much remains unknown. This review explores their structures and functions, aiming to spur novel metabolite discovery and advance drug development.

Fig. 1

Clustering of human microbiome metabolites based on related biosynthetic pathways and phylum origins.

Fig. 2

Different microorganisms derived from different niches in the human body (elements created using Servier Medical Art, licensed under CC BY 4.0).

Fig. 3

Structures of reuterin (1), β-hydroxypropionicacid (2), trimethylene glycol (3), mutanocyclin (4), reutericyclins A–C (5–7), 1-acetyl-β-carboline (8), and indole-3-lactic acid (9).

Fig. 4

Structures of hordatine B (10), quercetin 3-O-manoglucoside (11), 7’,8’-dihydro-8’-hydroxycitraniaxanthin (12), O-methylganoderic acid O (13), thalicsessine (14), austinol (15), and valdiate (16).

Fig. 5

Structures of 5-hydroxykynurenamine (17), 2S,4R-4-(9H-pyrido[3,4-b]indol-1-yl)-1,2,4-butanetriol (18), indoleacrylic acid (19), fortimicin A (20), stearic acid (21), myristic acid (22), p-mentha-1,3,5,8-tatraene (23), 6 hydroxypseudooxynicotine (24), _DL-glycerol 1-phosphate (25), 4-beta-D-glucan (26), L-theanine (27), L-fuculose (28), glycerol-1-propanoate (29), 5-butyltetrahydro-2-oxo-3-furancarboxylic acid (30), and 3,4,8-trihydroxy urolithin (31).

Fig. 6

Structures of cholic acid (32), deoxycholic acid (33), benzoic acid (34), phenyl acid (35), phenyl propionic acid (36), phenyl pyruvic acid (37), phenyl lactic acid (38), methyl benzene (39), 4-hydroxyphenyl acetic acid (40), 4-hydroxy benzoic acid (41), p-cresol (42), indole 3-acetic acid (43), indole 3-lactic acid (44), methyl indole (45), α-galactosylceramide (46), and propionic acid (47).

Fig. 7

Structures of ceramide phosphoinositol (48), dihydroceramides (49), galactosylceramide (50), 1-deoxydihydroceramide (51), ceramide phosphoethanolamine (52), 1-O-(α-D-galactosyl)-N-hexacosanoylphytosphingosine (KRN7000) (53), and GSL-Bf717 (54).

Fig. 8

Structures of N-(3-oxo-dodecanoyl)-l-homoserine lactone (3-oxo-C12-HSL) (55), pyocyanin (56), and phenazine (57).

Fig. 9

Structures of tilivalline (58), indole-3 acetic acid (59), 4-hydroxy phenyl lactate (60), trimethylamine-N-oxide (61), indoxyl sulfate (62), p-cresol sulfate (63), and imidazole propionate (64).

Fig. 10

Structures of butyric acid (65) and deoxycholic acid (66).

Fig. 11

Structures of phenylacetic acid (67), corynomycolic acid (68), and corynebactin (69).

Fig. 12

Structures of aurachin RE (70), aurachin C (71), heterobactin A and B (72 and 73), and humimycin A and B (74 and 75).

Fig. 13

Structures of phthiocerol dimycocerosate (76) and mycolactone polyketides A–D (77–80).

Fig. 14

Structures of brasilinolides A and B (81 and 82), nocardicyclins A and B (83 and 84), transvalencin Z (85), and nocobactin NA (86).

Fig. 15

Structures of JBIR-16 (87), nocardamine (88), asterobactin (89), and brasilibactin A (90).

Fig. 16

Structures of farnesol (91), YM-170320 (92), 3-methyladipic acid (93), tridecanoic acid (94), ethylmethylacetic acid (95), carnosine (96), D-gluconolactone (97), and L-threonine (98).

Fig. 17

Putative structures of nisin A and gassericin A.

Fig. 18

Structures of Microcin C7, C51, and C.