Structures and Biosynthetic Pathway of Coprisamides C and D, 2-Alkenylcinnamic Acid-Containing Peptides from the Gut Bacterium of the Carrion Beetle Silpha perforata

Abstract

Coprisamides C and D (1 and 2) were isolated from a gut bacterium, Micromonospora sp. UTJ3, of the carrion beetle Silpha perforata. Based on the combined analysis of UV, MS, and NMR spectral data, the planar structures of 1 and 2 were elucidated to be unreported derivatives of coprisamides A and B, cyclic depsipeptides bearing a 2-alkenylcinnamic acid unit and the unusual amino acids β-methylaspartic acid and 2,3-diaminopropanoic acid. The absolute configuration of 1 was determined using the advanced Marfey's method, phenylglycine methyl ester derivatization, and J-based configuration analysis. The biosynthetic gene clusters for the coprisamides were investigated based on genomic data from coprisamide-producing strains Micromonospora sp. UTJ3 and Streptomyces sp. SNU533. Coprisamide C (1) was active against the Mycobacterium tuberculosis mc 2 6230 strain.

Nyuzenamide C, an Antiangiogenic Epoxy Cinnamic Acid-Containing Bicyclic Peptide from a Riverine Streptomyces sp.

“…SNU533 of the dung beetle, Copris tripartitus , C and D; antitubercular compounds from the gut bacterium Micromonospora sp. UTJ3 of the carrion beetle, Silpha perforata ) as NRPs with an unusual acyl chain. , The incorporation of an epoxide unit into the cinnamic acid-derived acyl chain has been reported only once, with the antitubercular cyclic depsipeptide, NC-1, from red soil-derived Streptomyces sp. FXJ1.172, but this acyl chain differs from the alkyl chain present in 1,2-epoxypropyl cinnamic acid.…”

“…In particular, quinone reductase (QR) is a major phase II enzyme and is employed to determine chemoprevention activity of natural compounds . In our previous studies, coprisamides A–D, cyclic peptides with a cinnamic acid moiety, showed significant activity for induction of QR. , Based on the chemical structure of nyuzenamide C ( 1 ), which contained a cinnamic acid acyl chain in the structure, the effect of 1 on QR induction was determined. As a result, it was found that nyuzenamide C ( 1 ) increased the QR activity by 1.8-fold at a concentration of 20 μM without cytotoxicity in the Hepa-1c1c7 murine hepatoma cell line (Figure S19).…”

Azetidine-Bearing Non-Ribosomal Peptides, Bonnevillamides D and E, Isolated from a Carrion Beetle-Associated Actinomycete

“…found in the gut of Nicrophorus concolor 13 and antitubercular coprisamides containing βmethylaspartic acid and 2,3-diaminopropanoic acid isolated from Micromonospora sp. found on Silpha perforata, 14 which demonstrate their capability to produce structurally unique NRPs. Therefore, we further analyzed the metabolic profiles of carrion beetle-associated actinomycete strains in search of new bioactive NRPs using LC/MS.…”

Micromonospora: A Prolific Source of Bioactive Secondary Metabolites with Therapeutic Potential

“…Micromonospora strains are widely distributed in nature, inhabiting diverse environments such as terrestrial soils, 9−12 marine sediments, 13,14 mangrove forests, 15 plants, and animals. 16,17 At present, the genus Micromonospora consists of 110 species with validly published and correct names (http://www. bacterio.net/micromonospora.html), most of which are saprophytic, aerobic, and mesophilic.…”