Abstract
The initial sources of compounds that on a small scale exhibited interesting biological activities were confined to medium (a few kilograms) to larger scale (up to 100 kilograms or more) of the nominal organism. Over the last 10 plus years, this paradigm has moved to semisynthesis, total synthesis (sometimes of simpler versions) and the use of genomic techniques both to identify the source and then to utilize the data in due course. Examples will range from the early days with the arabinose-containing nucleosides, didemnins, through the ecteinascidins and halichondrins, and then to more current molecules derived from dolastatins that are now used as “warheads.
Highlights
The aim of this short review is to discuss bioactive compounds from marine organisms, focusing of the growing evidence that microorganisms associated with marine invertebrates, can be sources of the compounds isolated from these organisms
Didemnin B was pulled from clinical trials early in Phase II studies due to its significant toxicity, which with hindsight, might have been partially or totally due to the methodology used in those days [viz: single bolus dose at or close to the maximum tolerated level (MTD) in man]
It should be emphasized that bryostatin 1 is still one of the most potent biological agents tested in antitumor clinical trials, and as mentioned earlier, though the material used in trials sponsored by the NCI, initially came by isolation from massive shallow-water collections off the coast of California, such efforts are no longer necessary
Summary
The aim of this short review is to discuss bioactive compounds from marine organisms, focusing of the growing evidence that microorganisms associated with marine invertebrates, can be sources of the compounds isolated from these organisms. In a significant number of cases, such an involvement has been shown well after the initial reports, and in some cases, well after the compounds entered clinical trials, usually as putative anti-tumor compounds These reports have led to the view that there is a significant probability that a majority of bioactive compounds are produced by associated microbes, and not solely by the host invertebrate. This may well be the case with sponges, nudibranchs, tunicates, and some bryozoans, though as will be seen later under both the ecteinascidin and bryostatin headings, there is a strong probability that a mutually beneficial synergistic relationship exists between the host and a microbe producing a bioactive agent. The realization that such microbes, whether currently amenable to fermentation or as yet uncultured, are a major biosynthetic source of these bioactive agents, opens up the possibility of a larger scale production by use of suitable biotechnology approaches, aiding to solve the supply problem, and unravel their full potential
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