Two new spirotetronates have been isolated from the marine actinomycete Micromonospora sp. The new structures comprise a spiro-tetronic acid motif embedded within an eleven-membered macrocyclic core linked to a cyclohexene ring and trans- decalin moiety.
The strain CA-214671 was isolated from marine cave sediment in Gran Canaria (Spain). A BLASTN search in the Eztaxon database of the PCR-amplified 16S rRNA nucleotide sequence (1290 nt) indicated that the strain was closely related to Micromonospora chaiyaphumensis.
Phocoenamicins B and C (1 and 2), together with the known spirotetronate phocoenamicin (3), were isolated from cultures of Micromonospora sp. The acetone extract from this strain, isolated from marine sediments showed activity against methicillin-resistant Staphylococcus aureus (MRSA), Mycobacterium tuberculosis H37Ra and Mycobacterium bovis.
Bioassay-guided fractionation of this extract using SP207ss column chromatography and preparative reversed-phased HPLC led to the isolation of the new compounds 1 and two belonging to the spirotetronate class of polyketides.
The structures of the compounds were determined using a combination of HRMS, 1D, and 2D NMR experiments and comparison with the spectra reported for phocoenamicin.
Antibacterial activity tests of the pure compounds against these pathogens revealed minimal inhibitory concentration (MIC) values ranging from 4 to 64 μg / mL for MRSA, and 16 to 32 μg / mL for M. tuberculosis H37Ra.
There was no significant activity found against M. bovis and vancomycin-resistant Enterococcus faecium (VRE) at concentrations below 128 μg / mL, and weak activity detected against Bacillus subtilis grown on agar plates.
Phocoenamicins B (1) and C (2) showed antibacterial activity against Gram-positive bacteria. Compounds 1 and 3 showed significant activity against MRSA, one of the most common causes of hospital-acquired infections, while moderate to negligible activity was observed against M. tuberculosis H37Ra, M. bovis, B. subtilis and E. faecium VRE.
Additionally, moderate anti-tuberculosis activity against M. tuberculosis was displayed by 2 and 3. Apparently, conformational rigidity to achieve the proper orientation of the enone moiety could play a key role in the interaction with the target, revealing the possible structure-activity relationship for these compounds.
The study also confirms that Micromonospora species producing spirotetronates were widely spread within the marine environment.
The current studies by LC-MS of the strain collection point out that other Micromonospora strains producers of phocoenamicins have also been isolated from terrestrial environments.
The study highlighted that the marine environment offers enormous potential for the discovery of compounds with new chemical scaffolds, thus representing a great opportunity to find new antibiotics to confront multi-resistant bacteria.