The Genetic and Biochemical Basis of Polyketide Metabolism in Microorganisms and its Role in Drug Discovery and Development

C. Richard Hutchinson; C. W. Borell; M. J. Donovan; F. Kato; H. Motamedi; H. Nakayama; R. L. Rubin; S. L. Streicher; R. G. Summers; E. Wendt-Pienkowski; W. L. Wessel

doi:10.1055/s-2006-960227

Planta Med 1991; 57: S36-S43
DOI: 10.1055/s-2006-960227

Molecular Biology

The Genetic and Biochemical Basis of Polyketide Metabolism in Microorganisms and its Role in Drug Discovery and Development

C. Richard Hutchinson¹ , C. W. Borell¹ ^, ² , M. J. Donovan¹ ^, ³ , F. Kato¹ ^, ⁴ , H. Motamedi¹ ^, ⁵ , H. Nakayama¹ ^, ⁶ , R. L. Rubin¹ ^, ⁵ , S. L. Streicher¹ ^, ⁵ , R. G. Summers¹ , E. Wendt-Pienkowski¹ , W. L. Wessel¹

¹School of Pharmacy and Department of Bacteriology, University of Wisconsin, 425 N Charter St., Madison, Wisconsin 53706, U.S.A.
²Department of Microbiology, Ohio State University, Columbus, Ohio, U.S.A.
³Department of Molecular Genetics, Smith, Kline & French Laboratories, Swedeland, Pennsylvania, U.S.A.
⁴Department of Microbiology, School of Pharmaceutical Sciences, Toho University, Chiba, Japan
⁵Department of Infectious Disease, Merck, Sharpe & Dohme Research Laboratories, Rahway, New Jersey, U.S.A.
⁶Japan Research Institute, Sumitomo Pharmaceutical Co., Tokyo, Japan

Abstract

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Abstract

The possibilities for the design of new drug screening and development strategies directed to a specific objective on the basis of genetic engineering of microorganisms is discussed from two points of view. Firstly, results of work on genetic hybrids of Streptomyces species for the production of new metabolites such as mederrhodin (1) and aloespanoarin II (4) are described. Secondly, the enhanced production of known metabolites such as tetracenomycin A₂ (11) and tetracenomycin C (9) by recombinant Streptomyces species is considered. Mechanistic aspects of polyketide metabolism are included.

Key words

Microorganisms - polyketide metabolism - drug development - Streptomyces species - genetic engineering

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