A cyclopeptide and three oligomycin-class polyketides produced by an underexplored actinomycete of the genus Pseudosporangium

Abstract

Aside from the well-studied conventional actinomycetes such as Streptomyces, the less investigated genera of actinomycetes also represent a promising source of natural products. Genome mining indicated that members of the underexplored genus Pseudosporangium, from which no secondary metabolites have been reported to date, may harbor the biosynthetic machinery for the formation of novel natural products. The strain RD062863, that is available at a public culture collection, was obtained and subjected to metabolite analysis, which resulted in the discovery of a novel cyclopeptide, pseudosporamide (1), along with three new oligomycin-class polyketides, pseudosporamicins A–C (2–4). The unusual structure of compound 1, featured by a biaryl-bond bridging across a tripeptide scaffold, N-acetyl-ʟ-Tyr-ʟ-Pro-ʟ-Trp, was determined by a combination of spectroscopic analyses, chemical derivatization, ECD calculation, and DFT-based theoretical chemical shift calculation, revealing the presence of an (S a)-axial chirality around the biaryl bond. Compounds 2–4 lacked hydroxylation on the side chain of the spiroacetal rings, which showed clear contrast to other oligomycin congeners and related polyketides with ring-truncation or expansion. The new macrolides 2–4 displayed potent antimicrobial activity against the Gram-positive bacterium Kocuria rhizohpila and the plant pathogenic fungus Glomerella cingulata. All compounds showed moderate cytotoxicity against P388 murine leukemia cells with IC50 values in the micromolar to submicromolar ranges. These results exemplified the validity of phylogeny-focused strain selection combined with biosynthetic gene-directed genome mining for the efficient discovery of new natural products.

Unsaturated fatty acids and a prenylated tryptophan derivative from a rare actinomycete of the genus Couchioplanes

“…In a manner similar to a procedure from [ 21 ], to a solution of 6 (1.0 mg, 3.2 μmol) in dry N , N -dimethylformamide (100 μL) and N , N -diisopropylethylamine (10 μL) were added ( R )-PGME (1.9 mg, 9.6 μmol), PyBOP (3.6 mg, 7.0 μmol) and HOBt (1.0 mg, 7.4 μmol) at room temperature. After stirring for 3 h, ice-water was poured into the reaction mixture, which was then extracted with EtOAc.…”

“…Encouraged by these reports, we examined the metabolites of Pseudosporangium sp. RD062863, a strain available at the culture collection of the Biological Resource Center, National Institute of Technology and Evaluation (NBRC) [ 20 ], and discovered a novel cyclopeptide pseudosporamide along with three new oligomycin-class polyketide [ 21 ]. In addition, the same approach to the different family ( Pseudonocardiaceae ) yielded mycetoindole, a new class of dehydrotryptophan derivative from Actinomycetospora [ 22 ].…”

A biaryl-linked tripeptide from Planomonospora reveals a widespread class of minimal RiPP gene clusters

“…Brief Communication bond between the oxygen of Tyr-3 and C6 of Tyr-1 (Kase et al, 1987;Yasuzawa et al, 1987); OF-4949 (4) from Penicillinum rugulosum OF4949, which is identical to 3 except for asparagine in place of the central tyrosine and lack of the N-terminal acetyl group (Sano et al, 1986); and pseudosporamide (5) from Pseudosporangium sp. RD062863, reported while writing this article, with a Tyr-Pro-Trp sequence and a carbon-carbon bond between C6 of tyrosine and C-9 of tryptophan (Saito et al, 2020). Of note, compounds 3, 4, and 5 lack an absorption maximum at 315 nm.…”

“…We were unable to observe inhibition of different proteases by 1 (data not shown), suggesting that the amino acid sequence and/or ring size can strongly influence activity. 5 was reported to have weak cytotoxic activity (Saito et al, 2020).…”

Unsaturated fatty acids and a prenylated tryptophan derivative from a rare actinomycete of the genus Couchioplanes

“…Encouraged by these reports, we examined the metabolites of Pseudosporangium sp. RD062863, a strain available at the culture collection of Biological Resource Center, National Institute of Technology and Evaluation (NBRC) [20], and discovered a novel cyclopeptide pseudosporamide along with three new oligomycin-class polyketide [21]. In addition, the same approach to the different family (Pseudonocardiaceae) yielded mycetoindole, a new class of dehydrotryptophan derivative from Actinomycetospora [22].…”