Discovery of Kebanmycins with Antibacterial and Cytotoxic Activities from the Mangrove-Derived Streptomyces sp. SCSIO 40068

Mangrove derived actinomycetes are a rich reservoir of bioactive natural products and play important roles in pharmaceutical chemistry. In a screen of actinomycetes from mangrove rhizosphere sedimental environments, the isolated strain Streptomyces sp. SCSIO 40068 displayed strong antibacterial activity. Further fractionation of the extract yielded four new compounds kebanmycins A–D ( 1 – 4 ) and two known analogues FD-594 ( 5 ) and the aglycon ( 6 ). The structures of 1 – 6 were determined based on extensive spectroscopic data and single-crystal X-ray diffraction analysis. 1 – 3 featured a fused pyranonaphthaxanthene as an integral part of a 6/6/6/6/6/6 polycyclic motif, and showed bioactivity against a series of Gram-positive bacteria and cytotoxicity to several human tumor cells. In addition, the kebanmycins biosynthetic gene cluster ( keb ) was identified in Streptomyces sp. SCSIO 40068, and KebMT2 was biochemically characterized as a tailoring sugar- O -methyltransferase, leading to a proposed biosynthetic route to 1 – 6 . This study paves the way to further investigate 1 as a potential lead compound.