Methods for making polyketides using altered pks

Details Methods for making polyketides using altered pks Methods for making polyketides using altered pks

C - Chemistry, Metallurgy

12

N

C12N 15/52 (2006.01) C07C 327/30 (2006.01) C12N 9/10 (2006.01) C12N 15/62 (2006.01) C12P 19/62 (2006.01)

Patent

CA 2341640

The stereochemical centers of a polyketide can be changed by replacement of ketosynthase domains in the polyketide synthase (PKS) enzyme that produces the polyketide. The specificity of the AT domains of a PKS is determined by a hypervariable region that can be replaced or altered to change the specificity of the AT domain from a naturally occurring extender unit to another naturally or non-naturally occurring extender unit. Non-naturally occurring extender units, including methylmalonyl N-acetyl cysteamine thioester can be incorporated into polyketides in recombinant host cells or in cell-free systems to make polyketides.

On peut modifier les centres stéréochimiques d'un polycétide en remplaçant les domaines cétosynthase dans l'enzyme de polycétide synthase (PKS) qui produit le polycétide. On détermine la spécificité des domaines acyltransférase (AT) d'un polycétide synthase au moyen d'une région hypervariable qui peut être remplacée ou modifiée de façon à modifier la spécificité du domaine acyltransférase (AT) d'une unité d'extension naturelle en une autre unité d'extension naturelle ou non. On peut introduire les unités d'extension non naturelles, y compris du méthylmalonyl N-acétyle cystéamine thioester, dans des cellules hôtes de recombinaison ou des systèmes acellulaires, de façon à fabriquer des polycétides.

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