"Mutasynthesis couples the power of chemical synthesis with molecular biology to generate derivatives of medicinally valuable, natural products. Recently, this technique has been exploited by Cambridge-based biotech company Biotica Technology Ltd, and their collaborators, to generate promising new variants of the polyketide anti-cancer compounds rapamycin and borrelidin."
Mutasynthesis is basically precursor directed biosynthesis combined with mutagenesis of the producing strain. In this approach, one synthesizes analogues of an intermediate in a biosynthetic pathway and mutates the producing strain so that it can't provide the natural intermediate. Thus the rest of the pathway is forced to utilize the analogues. Pretty cool.
One of the fun things about science is the ability to make up new words. It makes us look smarter.
ReplyDeleteThese people do it quite well: Mutasynthesis, rapalogues (album title?).
They dont include any in vivo data or analysis, which i find very odd. There isnt any evidence to support their statements regarding the biological applications of this system.
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ReplyDelete^^ typo. where's the edit button
ReplyDeleteI'm sure they got sick of saying "rapamycin analogues" 10,000 times each day.
The point of the paper isn't that new drugs with improved activity have been identified, it's that "mutasynthesis" can be used to make privileged combinatorial libraries.
With precursor directed biosynthesis alone, there's a huge problem: various amounts of the natural product. Separating the natural product from the analogue isn't really amenable to high throughput screening.
Also, it's a review paper. The specifics are in the references, especially 11 and 12. It's implied that any specifics regarding the compounds' activities that aren't given are proprietary.