Abstract
Aromatic polyketides from marine actinomycetes have received increasing attention due to their unusual structures and potent bioactivities. Compared to their terrestrial counterparts, marine aromatic polyketides have been less discovered and their structural and biological diversities are far from being fully investigated. In this study, we employed a PCR-based genome mining method to discover aromatic polyketides in our marine bacteria collection. Five new atypical angucyclinones, fluostatins M-Q (1-5) featuring a unique 6-5-6-6 ring skeleton, were discovered from one "positive" Streptomyces sp. PKU-MA00045. The structures of fluostatins M-Q (1-5) were elucidated based on comprehensive spectroscopic analyses and the crystallographic structure of fluostatin P (4), which contains the most oxidized A-ring, was solved by X-ray diffraction analysis with Cu Kα radiation. Compared to the published 16 fluostatin analogues, fluostatins M-Q (1-5) contained a different methoxy group attached at C-7 and hydroxy group attached at C-4, enriching the structural diversity of aromatic polyketides from marine actinomycetes. Genome sequencing of Streptomyces sp. PKU-MA00045 revealed the biosynthetic gene cluster of fluostatins M-Q (1-5), which contained different genes and gene organizations compared to known fluostatin gene clusters, facilitating the investigation of the biosynthesis of the unique 6-5-6-6 ring skeleton in all fluostatins.