Angucyclines and Angucyclinones from Streptomyces sp. CB01913 Featuring C-Ring Cleavage and Expansion

Abstract

Angucyclines and angucyclinones are aromatic polyketides with a tetracyclic benz[a]anthracene skeleton. The benz[a]anthracene scaffold is biosynthesized by type II polyketide synthases that catalyze the decarboxylative condensation of a short acyl-CoA starter and nine extender units. Angucyclines and angucyclinones, the largest group of polycyclic aromatic polyketides, achieve structural diversity via subsequent oxidation, ring cleavage, amino acid incorporation, and glycosylation. We here report the discovery of 14 angucyclinones and two angucyclines (1–16) from Streptomyces sp. CB01913, identifying 12 new compounds featuring various oxidations on rings A and C (1, 2, and 4), different sugar moieties attached to rings A and B (3 and 6), and C-ring cleavage (5 and 10–14) and expansion (8). These new structural features, highlighted by C-ring cleavage and expansion, enrich the structural diversity of angucyclines and angucyclinones. All compounds were tested for cytotoxicity and antibacterial activities, with 1, 5, 15, and 16 showing moderate activities against selected cancer cell lines or bacterial strains.

New isofuranonaphthoquinones and isoindolequinones from Streptomyces sp. CB01883

“…It grows and sporulates well on ISP4 agar medium, and was classified as a Streptomyces species on the basis of a phylogenetic analysis using the concatenated partial sequences of three housekeeping genes 16 S rRNA, rpoB and trpB (Genebank accession number KT722854, KT736417 and KT793843, respectively). [14][15][16] In our continued effort Isofuranonaphthoquinones from Streptomyces sp. CB01883 Z Guo et al to study the biosynthesis of hybrid peptide-polyketide natural products, [19][20][21] we sequenced the genome of Streptomyces sp.…”

“…The NPLI biases natural products from Actinomycetales that are isolated from unexplored or underexplored ecological niches and unavailable in public strain collections. [7][8][9][10][11][12][13][14][15][16][17] The current library at TSRI consists of (i) purified natural products with fully assigned structures, (ii) C-18 mediumpressure liquid chromatography fractions, and (iii) crude extracts of microbial fermentation. Typically, strains were fermented in multiple media and subjected to HPLC and LC-MS analysis.…”

Competition and co-regulation of spirotoamide and tautomycetin biosynthesis in Streptomyces griseochromogenes, and isolation and structural elucidation of spirotoamide C and D

“…The assays were carried out by following previously reported methods and performed in the 96-well plates in duplicate with Müller-Hinton broth. 19,20 None of the compounds showed any activity at concentrations up to 100 μM.…”

Elmenols C-H, new angucycline derivatives isolated from a culture of Streptomyces sp. IFM 11490

“…1,5,6 Their structures are mainly based on the tetracyclic benz[a]anthracene skeleton. 7,8 In the continuation of our search for new bioactive natural products from actinomycetes, 9 we collected sea water and soil samples from different areas in Japan. Our laboratory reported the isolation of aotaphenazine 10 , sulfotanone 11 , yoropyrazone 12 and different pyranonaphtaquinone derivatives 13 from Streptomyces sps.…”

“…IFM 11490 and isolated isobenzofuran derivatives, named elmonin (7) as well as elmenols A (8) and B (9). 14 Further investigations of the culture of Streptomyces sp.…”