Title: Heterologous Production of Polyketides in<i>Streptomyces coelicolor</i>and<i>Escherichia coli</i>
Abstract: Heterologous Production of Polyketides in Streptomyces coelicolor and Escherichia coli James T. Kealey, James T. KealeySearch for more papers by this author James T. Kealey, James T. KealeySearch for more papers by this author Book Editor(s):Alan T. Bull, Alan T. Bull School of Biosciences, University of Kent, Canterbury, Kent, United KingdomSearch for more papers by this authorBeth Junker, Beth Junker Bioprocess Research and Development, Merck Research Laboratories, Rahway, New JerseySearch for more papers by this authorLeonard Katz, Leonard Katz SynBERC - Synthetic Biology Engineering Research Center, University of California-Berkeley, Emeryville, CaliforniaSearch for more papers by this authorLee R. Lynd, Lee R. Lynd Thayer School of Engineering, Dartmouth College, Hanover, New HampshireSearch for more papers by this authorPrakash Masurekar, Prakash Masurekar Department of Plant Biology & Plant Pathology, School of Environmental and Biological Sciences, Rutgers University, New Brunswick, New JerseySearch for more papers by this authorChristopher D. Reeves, Christopher D. Reeves Amyris Biotechnologies, Emeryville, CaliforniaSearch for more papers by this authorHuimin Zhao, Huimin Zhao Departments of Chemical and Biomolecular Engineering, Chemistry, and Bioengineering, Institute for Genomic Biology, Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, IllinoisSearch for more papers by this author First published: 25 March 2010 https://doi.org/10.1128/9781555816827.ch26 AboutPDFPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShareShare a linkShare onFacebookTwitterLinked InRedditWechat Summary This chapter reviews the development of heterologous polyketide production systems in Streptomyces coelicolor and Escherichia coli, providing specific examples of polyketides produced in these hosts to illustrate the utility of the approach. The first section covers S. coelicolor, an actinomycete that produces a number of polyketides, most notably the blue pigment actinorhodin. The success with S. coelicolor provided motivation to develop heterologous production systems in E. coli and Saccharomyces cerevisiae, user-friendly organisms for which advanced molecular biology tools and fermentation systems are available. In the second section, the development of an E. coli production system is described. Standard Streptomyces transformation methods are employed to introduce expression plasmids into S. coelicolor CH999, a strain that contains a chromosomal deletion of the actinorhodin gene cluster encoding the activities required for the synthesis of the aromatic polyketide actinorhodin. The epothilones are mixed polyketides/nonribosomal peptides that have microtubule-stabilizing activities similar to those of the taxanes but are active against Taxol-resistant tumors. Many polyketides, including epothilone and certain analogs of 6-deoxyerythronolide B (6Deb), are produced at low levels in the S. coelicolor heterologous production system. The availability of heterologous E. coli production systems, together with recent advances in synthetic biology, has accelerated studies of polyketide synthase (PKS) modularity and specificity. With further refinement of the connectivity rules, it is anticipated that virtually any polyketide can be produced in E. coli by coexpression of a suitable set of synthetic PKS modules. Manual of Industrial Microbiology and Biotechnology, Third Edition RelatedInformation
Publication Year: 2014
Publication Date: 2014-04-30
Language: en
Type: book-chapter
Indexed In: ['crossref']
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