Natural products from microbes associated with insects

Abstract

Here we review discoveries of secondary metabolites from microbes associated with insects. We mainly focus on natural products, where the ecological role has been at least partially elucidated, and/or the pharmaceutical properties evaluated, and on compounds with unique structural features. We demonstrate that the exploration of specific microbial-host interactions, in combination with multidisciplinary dereplication processes, has emerged as a successful strategy to identify novel chemical entities and to shed light on the ecology and evolution of defensive associations.

Keywords: biosynthesis; chemical ecology; natural products; secondary metabolism; structure elucidation; symbiosis.

Figure 1

Flow chart of the typical characterization of chemical signals from microbial interactions. (1) Chemical profiling of microbial interactions using analytical techniques. (2) Dereplication leads to potentially new small molecules. (3) Optimization of the isolation protocol based on biological assessment of the activity of the isolated compounds. (4) General conclusions about ecological role and evolution of interactions.

Figure 2

Multilateral microbe–insect interactions. (1) Insect–symbiont interactions with both partners benefiting from the interactions. (2) Antagonistic microbial interactions (e.g., competition for nutrients and space). (3) Antagonistic microbe–insect interactions (e.g., entomopathogenic microbes).

Figure 3

a) Interactions between bacterial (endo)symbionts and insects with both partners benefiting from the interactions (1). b) Defensive secondary metabolites isolated from bacterial symbionts: piericidin A1 (1), streptochlorin (2), pederin (3), and diaphorin (4).

Figure 4

Multilateral microbial interactions in fungus-growing insects. (1) Insect cultivar: protects and shares habitat and nutrients. (2) Cultivar antagonist: competition for nutrients and habitat. (3) Antagonist mutualist: competition for nutrients and habitat; detrimental infestation by antagonist. (4) Symbiont insect: (beneficial) coexistence by sharing and protecting habitat and nutrients.

Figure 5

Small molecules (chemical mediators) play key roles in maintaining garden homeostasis in fungus-growing insects: dentigerumycin (5), gerumycin A (6), gerumycin C (7), candicidin D (8), actinomycin D (9), antimycin A1 (10), pseudonocardone B (11), mycangimycin (12), frontalamide A (13), frontalamide B (14), and bacillaene A (15).

Figure 6

Secondary metabolites isolated from Actinobacteria from fungus-growing termites. Microtermolide A (16), microtermolide B (17), natalamycin A (18), 19-S-methylgeldanamycin (19), and 19-[(1S,4R)-4-hydroxy-1-methoxy-2-oxopentyl]geldanamycin (20).

Figure 7

Secondary metabolites from bacterial mutualists of solitary insects. Bafilomycin A1 (21), bafilomycin B1 (22), sceliphrolactam (23), tripartilactam (24), coprismycin A (25), collismycin A (26), dipyridine SF2738D (27), tripartin (28), and coprisamide A (29).

Figure 8

Beneficial interactions (1) between fungal symbionts and insects.

Figure 9

Secondary metabolites isolated from fungal symbionts. Cerulenin (30), helvolic acid (31), lepiochlorin (32), cyclo-(L-Pro-L-Leu) (33), bionectriol A (34), (+)-scleroderolide (35), dalesconol A (36), boydine B (37), boydene A (38), paraconfuranone A (39), and ilicicolinic acid A (40).

Figure 10

Predatory interactions, (1) entomopathogenic fungi use insect as prey.

Figure 11

Entomopathogenic fungi use secondary metabolites as insecticidal compounds to kill their prey. Destruxin A (41), serinocyclin A (42), beauvericin (43), and oosporein (44).