Salinamide F, new depsipeptide antibiotic and inhibitor of bacterial RNA polymerase from a marine-derived Streptomyces sp.

The marine environment is a rich source for unique actinomycete bacteria of significant biological and chemical diversity.^1,2 Marine-obligate and marine-derived actinomycetes have been shown to be the source of structurally diverse secondary metabolites, many of which have been shown to possess interesting anticancer properties.³ The discovery of antibiotics from this source is far less developed, but promising antibiotics such as anthracimycin provide significant motivation to explore this source further.⁴ Earlier, we showed that the marine-derived Streptomyces sp., strain CNB-091, produces a suite of at least five structurally unprecedented depsipeptides, salinamides A−E, that show significant antibacterial and anti-inflammatory properties.^5,6 Subsequently, salinamide A was shown to possess significant inhibitory activity against RNA polymerase (RNAP) from Gram-positive and Gram-negative bacteria.^7,8 As part of a collaborative program to further explore the chemical biology of the RNAP-inhibitory activity of the salinamides, we examined in more detail the extract and semi-purified fractions from the recultivation of Streptomyces sp. CNB-091 and report here the isolation of a new salinamide analog, salinamide F, which, like salinamide A, also possesses significant RNAP-inhibitory and antibacterial activity.

Streptomyces sp., strain CNB091, was isolated from a surface swab of a jellyfish (C. xamachana) collected in the Florida Keys in 1987 as previously described.⁵ The producing organism was cultured in forty 2.8 l Fernbach flasks each containing 1 l of a seawater-based medium (10 g starch, 4 g yeast extract, 2 g peptone, 1 g CaCO₃, 40 mg Fe₂(SO₄)₃-4H₂O, 100 mg KBr) by shaking at 230 r.p.m. at 27 °C for 7 days. At the end of the cultivation, sterilized XAD-16 resin (20 g l⁻¹) was added to adsorb the organic metabolites, and the culture and resin were shaken at 215 r.p.m. for 2 h. The resin and cell debris were filtered through cheesecloth, washed with deionized water and eluted with acetone. The acetone filtrate was concentrated under reduced pressure, and the resulting aqueous layer was extracted with ethyl acetate (3 × 500 ml). The ethyl acetate-soluble fractions were combined and reduced in vacuo to yield 3.5 g of extract from a 40 × 1 l culture.

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