Mycemycins A–E, New Dibenzoxazepinones Isolated from Two Different Streptomycetes

Abstract

Five new dibenzoxazepinone derivatives, mycemycins A–E (1–5), were isolated from the ethanol extracts of mycelia of two different streptomycetes. 1 and 2 were isolated from an acidic red soil-derived strain, Streptomyces sp. FXJ1.235, and 3–5 from a gntR gene-disrupted deep-sea strain named Streptomyces olivaceus FXJ8.012Δ1741. The structures of mycemycins were elucidated by a combination of spectroscopic analyses, including 1D- and 2D-NMR techniques.

Marine natural products

“…60 Following genetic manipulation of a marine Streptomyces olivaceus by disruption of orf-1741, a putative transcriptional gene, three halogenated dibenzoxazapinone derivatives, the mycemycins C-E 62-64, were isolated from the mutant strain and are the rst dibenzoxazapinones produced from a microbial source. 61 Marine Actinobacteria continue to surprise with the versatility of their biosynthetic machinery. Phylogenetic studies have led to the identication of 13 distinct marine actinomycete groups.…”

Identification and Characterization of Mycemycin Biosynthetic Gene Clusters in Streptomyces olivaceus FXJ8.012 and Streptomyces sp. FXJ1.235

“…sp. FXJ1.235 was reported previously [ 7 ]. Escherichia coli Top 10 was used for propagating plasmids and E. coli ET12567/pUZ8002 was used for conjugation between E. coli and streptomycetes.…”

“…GYM medium with 1 g/L NaCl was used as the fermentation medium for FXJ1.235, while modified R2 medium was used for FXJ8.012Δ1741. The culture conditions for mycemycin production were generally as described previously [ 7 ]. In short, spore suspensions were inoculated in 250 mL shake flasks containing 100 mL liquid GYM medium, which were then incubated as seed culture on a rotary shaker at 220 rpm and 28 °C for two days.…”

“…The mutants and wild type were fermented as mentioned above and the mycelium was extracted with enthanol as described previously [ 7 ].…”

“…In our previous work, we reported mycemycins A–E ( Figure 1 ) as new members of the DBP family with weak inhibitory activity on HIV-1 reverse transcriptase [ 7 ]. Mycemycins A and B were isolated from an acidic, red soil-derived strain Streptomyces sp.…”