This thesis details investigations of marine cyanobacterial secondary
metabolism, with emphasis on a strain of Phormidium sp. collected in Indonesia.
These studies assessed the effects of nineteen putative elicitor compounds on the
growth and metabolite production of five species of marine cyanobacteria,
biosynthetic investigation of an intriguing secondary metabolite, phormidolide,
and the discovery of one novel halogenated peptide, phormidamide.
The growth, biomass production and the ratio of the components of the
extract were affected by some of the elicitors in most of the cyanobacterial species
tested. However, production of a novel secondary metabolite or a significant
change in the bioactivity of the extracts was not observed.
Biosynthetic investigations of a brominated brine shrimp toxic polyketide,
phormidolide, were conducted on a cultured Phormidium sp. strain originally
isolated from Indonesia. Stable isotope feeding experiments confirmed its
polyketide nature and established a new example of a general trend in
cyanobacterial metabolism where both S-adenosyl methionine and C2 of acetate
contribute to the biogenesis of pendant methyl groups. At the same time, feedings
with deuterated acetate provided insight into the HMG-CoA synthase-like
mechanism by which addition of pendant methyl groups from C2 of acetate takes
Studies of phormidolide production in bromine-depleted medium showed
that two analogs are produced, debromophormidolide with a terminal olefin in
place of the vinyl bromide, and iodophormidolide, introducing iodine in place of
bromine from the trace amounts present in the medium. Supplementation of the
bromine-depleted culture medium with iodine resulted in a 10-fold increase of
iodophormidolide production, while bromine supplementation resulted in a more
moderate (2.5 fold) enhancement in phormidolide yield.
A novel halogenated cytotoxic peptide, phormidamide, was isolated and a
planar structure is proposed, pending confirmation by X-ray crystallographic
analysis. Phormidamide contains a unique bromophenylalanine functionality,
three chlorine atoms, and a very high number of quaternary carbon atoms which
have hindered structural elucidation efforts through spectroscopic methods. / Graduation date: 2004
|23 July 2003
|Vulpanovici, Florina Alexandra
|Gerwick, William H.
|Oregon State University
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