Hybrid polyketide synthases
The present invention provides for a polyketide synthase (PKS) capable of synthesizing an even-chain or odd-chain diacid or lactam or diamine. The present invention also provides for a host cell comprising the PKS and when cultured produces the even-chain diacid, odd-chain diacid, or KAPA. The present invention also provides for a host cell comprising the PKS capable of synthesizing a pimelic acid or KAPA, and when cultured produces biotin.
1. A non-naturally occurring polyketide synthase (PKS) that binds malonyl-CoA and releases malonic acid, wherein said non-naturally occurring PKS is a hybrid PKS comprising domains from two PKSs, and comprises a single, three-domain chimeric PKS module comprising a didomain containing a malonyl-specific acyltransferase (AT) domain linked to a cognate acyl carrier protein (ACP) domain, and a type I thioesterase (TE) domain linked to said didomain;
wherein said didomain is from a load module from a PKS selected from the group consisting of a Streptomyces bikiniensis chalcomucin PKS, a Streptomyces caelestis niddamycin PKS, a Streptomyces avermitilis oligomycin PKS, and a Sorangium cellulosum epothilone PKS; and
wherein said TE domain is from a Streptomyces venezuelae pikromycin PKS or a Saccharopolyspora erythraea erythromycin PKS.