Abstract
The diversity of actinomycetes associated with the marine sponge Coscinoderma mathewsi collected from Hurghada (Egypt) was studied. Twenty-three actinomycetes were separated and identified based on the 16S rDNA gene sequence analysis. Out of them, three isolates were classified as novel species of the genera Micromonospora, Nocardia, and Gordonia. Genome sequencing of actinomycete strains has revealed many silent biosynthetic gene clusters and has shown their exceptional capacity for the production of secondary metabolites, not observed under classical cultivation conditions. Therefore, the effect of mycolic-acid-containing bacteria or mycolic acid on the biosynthesis of cryptic natural products was investigated. Sponge-derived actinomycete Micromonospora sp. UA17 was co-cultured using liquid fermentation with two mycolic acid-containing actinomycetes (Gordonia sp. UA19 and Nocardia sp. UA 23), or supplemented with pure mycolic acid. LC-HRESIMS data were analyzed to compare natural production across all crude extracts. Micromonospora sp. UA17 was rich with isotetracenone, indolocarbazole, and anthracycline analogs. Some co-culture extracts showed metabolites such as a chlorocardicin, neocopiamycin A, and chicamycin B that were not found in the respective monocultures, suggesting a mycolic acid effect on the induction of cryptic natural product biosynthetic pathways. The antibacterial, antifungal, and antiparasitic activities for the different cultures extracts were also tested.
Highlights
Actinomycetes are Gram-positive bacteria living in a wide range of aquatic, terrestrial environments and produce a variety of diverse bioactive compounds [1,2,3,4]
UA 23) and monocultures amended with mycolic acid were more active against Staphylococcus aureus NCTC 8325, Enterococcus faecalis, and Candida albicans 5314 compared with monoculture extracts, where UA17 + UA23 had recorded the highest inhibition activities with minimal inhibitory concentration (MIC) value of 4.2, 3.9, and 3.8 μg/mL, respectively (Table 4)
The rapidly growing number of actinomycete genome sequences highlighted their potential for biosynthesizing a plethora of natural products that are much higher than expected during classical laboratory conditions
Summary
Actinomycetes are Gram-positive bacteria living in a wide range of aquatic, terrestrial environments and produce a variety of diverse bioactive compounds [1,2,3,4]. 2011, reported the induction of a red pigment by Streptomyces lividans TK23 after co-cultivation with living cells of the mycolic acid-containing bacterium Tsukamurella pulmonis TP-B0596 [40]. It was shown that the metabolite profiles of several Streptomyces strains were changed after co-cultivation with the mycolic acid-containing bacterium T. pulmonis. Arcyriaflavin E, a new cytotoxic indolocarbazole alkaloid, was isolated by co-cultivation of mycolic acid-containing bacteria and Streptomyces cinnamoneus NBRC 13823 [42]. Cultivated with mycolic acid-containing bacterium Tsukamurella pulmonis TP-B0596 [43] These studies highlight the efficacy of the co-cultivation strategy with mycolic acid-containing bacteria, for the discovery of cryptic natural products. Isolates of novel species belonging to the genera Micromonospora, Nocardia, and Gordonia were identified, and the effect of pure mycolic acid and mycolic acid-containing bacteria actinomycete Gordonia sp. The isolates were maintained on plates at the fridge and in 20% glycerol at −80 ◦C
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