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Secondary metabolites of bacteria obtained from the northeastern Pacific ocean : structure elucidation and biosynthetic studies

University of British Columbia

Investigation of the organic extracts obtained from cultures of four species of bacteria isolated from the northeastern Pacific ocean led to the isolation of eight new and six previously known secondary metabolites. The structures of the new compounds were elucidated by extensive spectroscopic analysis. In addition, the biogenetic origins of the atoms in two of the bacterial metabolites were probed using stable isotope incorporation experiments. A culture of the bacterium Serratia odorifera, isolated from a surface water sample taken near a Chinook salmon (Oncorhyncus tshawytscha) farm in Georgia Strait, British Columbia, produced the novel compound oncorhyncolide (34). Oncorhyncolide has a unique structure that is apparently not related to other known microbial metabolites isolated from terrestrial sources. Biosynthetic studies using stable isotopes have shown that all the carbons in oncorhyncolide are derived from acetate. The methyl branches in oncorhyncolide are derived from the C2 of acetate and are attached to carbon atoms derived from the carbonyl carbon, C1, of an acetate unit. This type of methyl branching is very rare in polyketide biosynthesis. Examination of the ethyl acetate extracts of a solid agar culture of Pseudomonas fluorescens obtained from an unidentified tunicate in Moira Sound, Alaska, led to the isolation of moiramides A (38), B (39) and C (40) as well as the known compound andrimid (41). The crude extract had shown antibacterial activity against Staphylococcus aureus and methicillinresistant S. aureus. Moiramide B and andrimid proved to be the compounds responsible for this activity. Biosynthetic studies on andrimid have shown that the acylsuccinimide ring is derived from valine, glycine and acetate. It has been proposed that the biosynthesis proceeds through a dipeptide-like intermediate formed from γ-amino-β-keto acids that are in turn formed from valine and glycine homologated with acetate, presumably via malonyl-CoA. Liquid cultures of Pseudomonas sp. 91V47 obtained from an abalone collected off Cortez Island in Georgia Strait, British Columbia, gave an extract that exhibited potent in vitro cytotoxicity. Bioassay-guided fractionation of the crude extract led to the isolation of three new δ-hydroxy acid rhizoxin analogs (44 to 46). The three new compounds showed significant in vitro activity against P388 murine leukemia. A marine isolate of the bacterium Bacillus pumilus, obtained from a sediment sample collected in Georgia Strait, British Columbia, produced an extract that exhibited antimicrobial activity against Staphylococcus aureus, methicillin-resistant S. aureus and S. saprophytics. The known compound AI-77-B (54), previously isolated from terrestrial and marine sources of B. pumilus, was found to be responsible for the antibacterial activity in the crude extract. A new AI-77-B analog, compound 57, was also isolated. Compound 57 showed antibacterial activity only at high concentrations. [chemical compound diagrams]

Thesis/Dissertation

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2009-04-08

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http://hdl.handle.net/2429/6954

Chemistry

University of British Columbia

UBCV

DSpace