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Applied and Environmental Microbiology, November 2003, p. 6698-6702, Vol. 69, No. 11
0099-2240/03/$08.00+0     DOI: 10.1128/AEM.69.11.6698-6702.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Biosynthesis of Yersiniabactin, a Complex Polyketide-Nonribosomal Peptide, Using Escherichia coli as a Heterologous Host

Blaine A. Pfeifer,1 Clay C. C. Wang,1 Christopher T. Walsh,2 and Chaitan Khosla3,4*

Chemical Engineering,1 Chemistry,3 Biochemistry, Stanford University, Stanford, California 94305,4 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 021152

Received 20 June 2003/ Accepted 18 August 2003

The medicinal value associated with complex polyketide and nonribosomal peptide natural products has prompted biosynthetic schemes dependent upon heterologous microbial hosts. Here we report the successful biosynthesis of yersiniabactin (Ybt), a model polyketide-nonribosomal peptide hybrid natural product, using Escherichia coli as a heterologous host. After introducing the biochemical pathway for Ybt into E. coli, biosynthesis was initially monitored qualitatively by mass spectrometry. Next, production of Ybt was quantified in a high-cell-density fermentation environment with titers reaching 67 ± 21 (mean ± standard deviation) mg/liter and a volumetric productivity of 1.1 ± 0.3 mg/liter-h. This success has implications for basic and applied studies on Ybt biosynthesis and also, more generally, for future production of polyketide, nonribosomal peptide, and mixed polyketide-nonribosomal peptide natural products using E. coli.

* 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.

Applied and Environmental Microbiology, November 2003, p. 6698-6702, Vol. 69, No. 11
0099-2240/03/$08.00+0     DOI: 10.1128/AEM.69.11.6698-6702.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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