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Biotech / Medical : Kosan BioSciences -- KOSN -- Ignore unavailable to you. Want to Upgrade?


To: Icebrg who wrote (608)10/8/2005 7:22:48 AM
From: Mike McFarland  Respond to of 933
 
recent theoretical study has revealed that modular PKSs
(such as the erythromycin PKS) have the potential to generate
hundreds of millions of compounds through reassembly of the
catalytic units in novel combinations*. This is a staggering
number compared with the 10,000 polyketides described from
all natural sources.


The Lego-ization of polyketide biosynthesis
David H Sherman
nature.com

*Theoretical Considerations and Computational
Analysis of the Complexity in Polyketide Synthesis Pathways
Joanna González-Lergier, Linda J. Broadbelt,
and Vassily Hatzimanikatis

pubs.acs.org
...experimental approaches to engineer novel polyketides,
a number of which will likely have medicinal properties



To: Icebrg who wrote (608)5/26/2006 2:52:32 PM
From: tuck  Read Replies (1) | Respond to of 933
 
[Activating hybrid modular interfaces in synthetic polyketide synthases by cassette replacement of ketosynthase domains]

>>Chem Biol. 2006 May;13(5):469-74.

Activating hybrid modular interfaces in synthetic polyketide synthases by cassette replacement of ketosynthase domains.

Chandran SS, Menzella HG, Carney JR, Santi DV.

Kosan Biosciences, Inc., 3832 Bay Center Place, Hayward, California 94545.

Unnatural combinations of polyketide synthase modules often fail to make a polyketide product. The causes of these failures are likely complex and are not yet amenable to rational correction. One possible explanation is the inability of the ketosynthase (KS) domain to extend the ketide donated to it by the upstream module. We therefore addressed the problem by exchanging KS domains of the acceptor module in a combinatorial fashion and coexpressing these chimeric modules with ketide-donor modules that naturally interact with the transplanted KS. This approach was remarkably successful in activating previously unproductive bimodular combinations, and the results augur well for the ongoing development of molecular tools to design and produce novel polyketides.<<

Cheers, Tuck