Here, we describe two -acetyl-cysteinylated streptophenazines ( and ) produced by the soil-derived sp. ID63040 and identified through a metabolomic approach. These metabolites attracted our interest due to their low occurrence frequency in a large library of fermentation broth extracts and their consistent presence in biological replicates of the producer strain. The compounds were found to possess broad-spectrum antibacterial activity while exhibiting low cytotoxicity. The biosynthetic gene cluster from sp. ID63040 was found to be highly similar to the streptophenazine reference cluster in the MIBiG database, which originates from the marine sp. CNB-091. Compounds and were the main streptophenazine products from sp. ID63040 at all cultivation times but were not detected in sp. CNB-091. The lack of obvious candidates for cysteinylation in the sp. ID63040 biosynthetic gene cluster suggests that the -acetyl-cysteine moiety derives from cellular functions, most likely from mycothiol. Overall, our data represent an interesting example of how to leverage metabolomics for the discovery of new natural products and point out the often-neglected contribution of house-keeping cellular functions to natural product diversification.
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http://dx.doi.org/10.1021/acs.jnatprod.1c01123 | DOI Listing |
Mar Drugs
December 2023
CAS Key Laboratory of Tropical Marine Bio-Resources and Ecology, RNAM Center for Marine Microbiology, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China.
The one strain many compounds (OSMAC) strategy is an effective method for activating silent gene clusters by cultivating microorganisms under various conditions. The whole genome sequence of the marine-derived strain SCSIO LCY30 revealed that it contains 30 biosynthetic gene clusters (BGCs). By using the OSMAC strategy, three types of secondary metabolites were activated and identified, including three angucyclines, mayamycin A (), mayamycin B (), and rabolemycin (); two streptophenazines (streptophenazin O () and M ()); and a macrolide dimeric dinactin (), respectively.
View Article and Find Full Text PDFJ Antibiot (Tokyo)
October 2023
Chemical Sciences and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram, 695019, Kerala, India.
Cocultivation of combinations of Streptomyces species isolated from the same soil was explored to isolate novel secondary metabolites. Recently, we reported the isolation of a novel vicinal diepoxide of alloaureothin along with three carboxamides, 4-aminobenzoic acid, and 1,6-dimethoxyphenazine from the individual culture of Streptomyces luteireticuli NIIST-D31. Herein, cocultivation of NIIST-D31 with Streptomyces luteoverticillatus NIIST-D47 afforded two new stereochemical variants of streptophenazine (S1 and S2), and 1-N-methylalbonoursin, where the individual culture of NIIST-D47 primarily produced carbazomycins A, D, and E.
View Article and Find Full Text PDFNat Prod Res
February 2017
a Ocean College, Zhoushan Campus , Zhejiang University, Zhoushan , China.
Six phenazines including three new ones were isolated from the culture of a marine actinomycete Streptomyces sp. 182SMLY. Based on the analyses of NMR, HRESIMS, optical rotation value, and CD data, the structures of these isolated compounds were determined as new phenazines of (-)-streptophenazines M-O and known phenazines of 1-carbomethoxyphenazine and (-)-streptophenazines A and B.
View Article and Find Full Text PDFMar Drugs
March 2014
Kiel Center for Marine Natural Products at the Helmholtz Center for Ocean Research (GEOMAR), Am Kiel-Kanal 44, Kiel 24106, Germany.
Eight streptophenazines (A-H) have been identified so far as products of Streptomyces strain HB202, which was isolated from the sponge Halichondria panicea from the Baltic Sea. The variation of bioactivities based on small structural changes initiated further studies on new derivatives. Three new streptophenazines (I-K) were identified after fermentation in the present study.
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