Hybrid polyketide synthases and novel loading domains

Chemistry: molecular biology and microbiology – Enzyme – proenzyme; compositions thereof; process for...

Reexamination Certificate

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C536S023200

Reexamination Certificate

active

07148045

ABSTRACT:
A polyketide synthase (“PKS”) of Type I is a complex multienzyme including a loading domain linked to a multiplicity of extension domains. The first extension module receives an acyl starter unit from the loading domain and each extension module adds a further ketide unit which may undergo processing (e.g. reduction). We have found that the Ksq domain possessed by some PKS's has decarboxylating activity, e.g. generating (substituted) acyl from (substituted) malonyl. The CLF domain of type II PKS's has similar activity. By inserting loading modules including such domains into PKS's not normally possessing them it is possible to control the starter units used.

REFERENCES:
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patent: 5712146 (1998-01-01), Khosla et al.
Kuhstoss et al. Production of a novel polyketide through the construction of a hybrid polyketide synthase. Gene (1996) 183:231-236.
Khosia C. Harnessing the Biosynthetic Potential of Modular Polyketide Synthases. Chemical Reviews (1997) 97:2577-2590.
Marsden et al. Engineering Broader Specificity into an Antibiotic-Producing Polyketide Synthase. Science (Jan., 1998) 279: 199-202.
Oliynyk et al. A hybrid modular polyketide synthase obtained by domain swapping. Chem. Biol. (1996) 10: 833-839.

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