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Metabolic engineering for drug discovery and development

Abstract

Metabolic engineering has been defined as the redirection of metabolic pathways using genetic manipulation. Since the emergence of metabolic engineering science in the early 1980s, the field has made notable strides not only at a conceptual level, but also with regard to translating these concepts into practical products and processes. Today, metabolic engineering plays an important role in the generation of fuels from renewable resources, the conversion of agricultural raw materials (for example, corn syrup) into bulk and specialty chemicals, and the discovery, development and scale-up of therapeutically useful products. This article focuses on recent advances in the last category. Specifically, we review the impact that converging developments in genetic engineering and biosynthetic chemistry are having on natural-product drug discovery.

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Figure 1: Examples of natural product drugs.
Figure 2: Isoprenoid biosynthesis.
Figure 3: Polyketide biosynthesis.

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Acknowledgements

Research in the authors labs has been supported by grants from the National Institutes of Health (to C.K.) and National Science Foundation, Office of Naval Research, Maxygen, Diversa, and the University of California Discovery Grant Program (to J.D.K.).

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Chatian Khosla is a founder of Kosan Biosciences, Inc, which discovers and develops new natural-product drugs. Jay D. Keasling has received funding from Maxygen, Codexis, Inc. and Diversa Corp. for work related to this article.

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Polyketides

terpenoids: higher

Detection and Analysis of Polyketide Synthase Domains

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Khosla, C., Keasling, J. Metabolic engineering for drug discovery and development. Nat Rev Drug Discov 2, 1019–1025 (2003). https://doi.org/10.1038/nrd1256

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