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Microbiology and Molecular Biology Reviews, March 2001, p. 106-118, Vol. 65, No. 1
1092-2172/01/$04.00+0   DOI: 10.1128/MMBR.65.1.106-118.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Biosynthesis of Polyketides in Heterologous Hosts

Blaine A. Pfeifer1 and Chaitan Khosla1,2,3,*

Departments of Chemical Engineering,1 Chemistry,2 and Biochemistry,3 Stanford University, Stanford, California 94305-5025

Polyketide natural products show great promise as medicinal agents. Typically the products of microbial secondary biosynthesis, polyketides are synthesized by an evolutionarily related but architecturally diverse family of multifunctional enzymes called polyketide synthases. A principal limitation for fundamental biochemical studies of these modular megasynthases, as well as for their applications in biotechnology, is the challenge associated with manipulating the natural microorganism that produces a polyketide of interest. To ameliorate this limitation, over the past decade several genetically amenable microbes have been developed as heterologous hosts for polyketide biosynthesis. Here we review the state of the art as well as the difficulties associated with heterologous polyketide production. In particular, we focus on two model hosts, Streptomyces coelicolor and Escherichia coli. Future directions for this relatively new but growing technological opportunity are also discussed.

* Corresponding author. Mailing address: Department of Chemical Engineering, Stanford University, Stanford, CA 94305-5025. Phone and Fax: (650) 723-6538. E-mail: ck{at}chemeng.stanford.edu.

Microbiology and Molecular Biology Reviews, March 2001, p. 106-118, Vol. 65, No. 1
1092-2172/01/$04.00+0   DOI: 10.1128/MMBR.65.1.106-118.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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