Precursor-directed biosynthesis of epothilone in Escherichia coli.

Precursor-directed biosynthesis of epothilone in Escherichia coli. Research Abstract Details 

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Precursor-directed biosynthesis of epothilone in Escherichia coli. Abstract Text:

Christopher N Boddy,Kinya Hotta,Martha Lovato Tse,R Edward Watts,Chaitan Khosla,

Engineered biosynthetic pathways provide a powerful method for generating complex molecules. Precursor-directed biosynthesis, which combines chemical synthesis and enzymatic transformations, allows non-native starting materials to be incorporated into biosynthetic pathways. Using this approach, we achieved the production of the anticancer agent epothilone C in Escherichia coli. An E. coli strain was engineered to express the last three modules of the epothilone biosynthetic pathway (epoD-M6, epoE, and epoF) and the substrate required to complement the biosynthetic enzymes was obtained by chemical synthesis. Under high-density cell culture conditions, the E. coli strain processed exogenously fed synthetic substrate into epothilone C at levels comparable to the native host (1 mg/L) and at higher levels than other heterologous hosts. Importantly, this precursor-directed approach will allow chemical modifications to be introduced into the polyketide backbone and may ultimately provide access to epothilone analogues with improved pharmacological properties in quantities sufficient for clinical development.

Precursor-directed biosynthesis of epothilone in Escherichia coli. Publishing Authors By Initials

CN Boddy,K Hotta,ML Tse,RE Watts,C Khosla,

For similar proteins: protein precursors research abstracts see: proteins: protein precursors research

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Precursor-directed biosynthesis of epothilone in Escherichia coli. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Journal of the American Chemical Society

VOLUME: 126

Page Numbers: 7436-7

Journal Abbreviation: J. Am. Chem. Soc.

ISSN: 0002-7863

DAY: 23

MONTH: Jun

YEAR: 2004

Precursor-directed biosynthesis of epothilone in Escherichia coli. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7503056

Precursor-directed biosynthesis of epothilone in Escherichia coli. Keywords Mesh Terms:

KEYWORDS: Protein Precursors

MESH TERMS: physiology

Chemical & Substance for Abstract: Precursor-directed biosynthesis of epothilone in Escherichia coli. Information

Substance Name: epothilone C

Registry Number: 0

Grant and Affiliation Information for Precursor-directed biosynthesis of epothilone in Escherichia coli.

AFFILIATION: Departments of Chemical Engineering, Chemistry, and Biochemistry, Stanford University, Stanford, California 94305-5025, USA.

Country: United States

AGENCY: United States NCI

GRANT: F32 CA091636

ACRONYM: CA

MEDLINETA: J Am Chem Soc

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