Leland Stanford Junior University

Other

The John Innes Institute

Kosan Biosciences Incorporated

Brown University

The John Innes Centre

The Johns Innes Institute

Camilla M Kao

Chaitan Khosla

Robert G McDaniel

Hong Fu

David A Hopwood

Suzanne Ebert-Khosla

Guanglin Luo

Rembert Pieper

David E Cane

Gary W Ashley

Susanne Ebert-Khosla

Combinatorial libraries of polyketides can be obtained by suitable manipulation of a host modular polyketide synthase gene cluster such as that which encodes the PKS for erythromycin. The combinatorial library is useful as a source of pharmaceutically active compounds. In addition, novel polyketides and antibiotics are prepared using this method.

Polyketides and antibiotics produced by combinatorial techniques

Novel polyketides and novel methods of efficiently producing both new and known polyketides, using recombinant technology, are disclosed. In particular, a novel host-vector system is described which is used to produce polyketide synthases which in turn catalyze the production of a variety of polyketides.

Recombinant production of novel polyketides

A polyketide or glycosylated polyketide which has the formula:wherein R* is methyl or ethyl;each of R-Ris methyl;Xis OH or H; and/orXis=O, OH or H;Xis OH or H;Xis OH or H;a pi bond is present at positions 10-11, 8-9, 4-5 and/or 2-3; and wherein at least one of the following characteristics is present:Xis H;Xis OH or H;Xis H;Xis H; ora pi bond is present at positions 10-11, 8-9, 4-5 and/or 2-3.

Macrolide analogs

Methods to prepare cells comprising heterologous polyketide synthase expression systems

A polyketide, or an antibiotic which is obtainable from the polyketide by a method comprising treating the polyketide with a culture medium conditioned by , selected from the group consisting of:

Method to produce novel polyketides

Combinatorial polyketide libraries produced using a modular PKS gene cluster as scaffold

Combinatorial libraries of polyketides can be obtained by suitable manipulation of a host modular polyketide synthase gene cluster such as that which encodes the PKS for erythromycin. The combinatorial library is useful as a source of pharmaceutically active compounds.

Modified modular PKS with retained scaffold

Cell-free systems which effect the production of polyketides employing modular polyketide synthases are described. Libraries of new and/or known polyketides may also be produced in cell-free systems employing aromatic PKS, modular PKS or both.

Cell-free synthesis of polyketides

Modified PKS gene clusters which produce novel polyketides in an efficient system in a host cell or in a cell free extract are described.

Growing community of inventors

Palo Alto, CA, United States of America

Camilla M Kao