Zelkovamycins B–E, Cyclic Octapeptides Containing Rare Amino Acid Residues from an Endophytic Kitasatospora sp

Abstract

Four unusual cyclopeptides, zelkovamycins B–E (1–4), were isolated from an endophytic Kitasatospora sp. Zelkovamycin B was featured by an unprecedented 3-methyl-5-hydroxy­pyrrolidine-2,4-dione ring system linked to the cyclopeptide skeleton. Their structures and full configurations were established by spectroscopic analysis, Marfey’s method, and NMR calculations. A plausible biosynthetic pathway for zelkovamycins was proposed based on gene cluster analysis. Zelkovamycin E displayed potent inhibitory activity against H1N1 influenza A virus.

Comparative Genomic Insights Into the Taxonomic Classification, Diversity, and Secondary Metabolic Potentials of Kitasatospora, a Genus Closely Related to Streptomyces

“…It has also been shown that Streptomyces genomes are recombinogenic, with a high recombination rate exceeding those observed within many other bacterial species ( Doroghazi and Buckley, 2010 ). As the sister genus of Streptomyces , Kitasatospora has gradually attracted people’s attention ( Hao et al, 2020 ; Kim et al, 2020 ; Yun et al, 2020 ). So far, at least 50 bioactive compounds have been discovered from Kitasatospora strains ( Takahashi, 2017 ), such as setamycin, kitasetaline, and satosporin ( Ōmura et al, 1981 ; Aroonsri et al, 2012 ; Arens et al, 2013 ), exhibiting a wide range of bioactivities (e.g., antifungal, herbicidal, antitumor).…”

Actinomadura graeca sp. nov.: A novel producer of the macrocyclic antibiotic zelkovamycin

“…Following the completion of this work and during the preparation of this manuscript, the isolation of zelkovamycin and its four analogues zelkovamycin B-E from Kitasatospora sp. CPCC204717 [ 62 ] was reported. In this study, a putative biosynthetic cluster for the five peptides was proposed, which largely agrees with the model described in the present work.…”

Acremopeptaibols A–F, 16-Residue Peptaibols from the Sponge-Derived Acremonium sp. IMB18-086 Cultivated with Heat-Killed Pseudomonas aeruginosa

“…Mueller-Hinton medium (0.6% beef extract, 1.75% acid hydrolysate of casein, 0.15% starch) as described previously. 17 Cytotoxicity Assay. Cell viability was evaluated by using the Cell Counting Kit-8 (CCK8, Meilunbio, China) assay as described previously.…”

“…Co-culturing different microbes in a single environment is an effective approach to enhance the chemical diversity of metabolites. − Co-cultivation (also called mixed fermentation) can create a competitive environment, which may activate silent secondary metabolism genes and lead to the biosynthesis of bioactive products responsible for chemical defense. − An increasing number of co-culture experiments have led to the discovery of new antimicrobials or to enhanced accumulation of metabolites even in the absence of viable bacterial cells. − The study by Mearns-Spragg et al showed that (co-)­cultivation of marine microorganisms with live or dead bacteria both could stimulate the production of antimicrobial activity, and in most cases there was no difference in antimicrobial activity induced by live and dead cells . As a part of our ongoing search for new antimicrobials, − we carried out (co-)­cultivation experiments of sponge-derived fungi with different live bacteria ( Escherichia coli and Bacillus subtilis ), actinomycetes, and other fungi or with autoclaved Pseudomonas aeruginosa , to elicit the production of fungal metabolites. Because P. aeruginosa is an opportunistic pathogen, the use of heat-killed P. aeruginosa in the mixed cultivation can offer a safe experimental condition and also reduce interexperiment variation. , Herein, we report the identification of six new peptaibols ( 1 – 6 ) and five known compounds from the sponge-associated fungus Acremonium sp.…”