Antimicrobial Trioxacarcin 1,2-Dihydroxyanthraquinones from the Bacterium Streptomyces sp. 127Q Isolated from the Stingless Bee Tetragonula carbonaria.

In contrast to honeybees, the Australian stingless bee Tetragonula carbonaria appears to be robust against microbial pathogens. Streptomyces sp. 127Q, isolated from T. carbonaria, inhibited the growth of Lysinibacillus sphaericus, which is the only microorganism reported to affect T. carbonaria. The antimicrobials were purified from Streptomyces sp. 127Q by bioassay-guided isolation using ethyl acetate extraction and Diaion HP20 chromatography, followed by reverse phase HPLC fractionation. The antimicrobial compounds were identified by high-resolution mass spectrometry, UV-Vis-spectroscopy, nuclear magnetic resonance spectroscopy, and genome mining as new members of the trioxacarcin/gutingimycin family having a 1,2-dihydroxyanthraquinone aromatic core structure. A closely related gutingimycin with a 1,2-dihydroxyanthraquinone moiety was previously observed in a crystallisation experiment of trioxacarcin A with an oligonucleotide. Streptomyces sp. 127Q produces a wide range of trioxacarcins/gutingimycins. At the onset of trioxacarcins production, Streptomyces sp. 127Q appeared to rapidly convert trioxacarcin epoxides with water, guanine, and nicotinic acid. The 1,2-dihydroxyanthraquinone trioxacarcins, trioxacarcin 692 and trioxacarcin 780, inhibited L. sphaericus with minimal inhibitory concentrations (MICs) of 37.5 μM and 75 μM, respectively. The MIC against Escherichia coli and Staphylococcus aureus was 75 μM and 150 μM, respectively. In the photoantimicrobial screening, the MIC for trioxacarcin 692 against E. coli and S. aureus decreased by 8-fold, and for trioxacarcin 780 by 4-fold. Following light pretreatment, trioxacarcin 692 (9.4 μM) inhibited E. coli and S. aureus at concentrations comparable to those of the established antibiotics ciprofloxacin and vancomycin. Neisseria gonorrhoeae was only inhibited at an MIC of ca. 18.8 μM after light preincubation. The 1,2-dihydroxyanthraquinone trioxacarcins constitute powerful antimicrobial compounds belonging to the trioxacarcin/gutingimycin family.