Letter abstract
Nature Chemical Biology 2, 423 - 428 (2006)
Published online: 25 June 2006 | doi:10.1038/nchembio803
Total biosynthesis of antitumor nonribosomal peptides in Escherichia coli
Kenji Watanabe1, Kinya Hotta1, Alex P Praseuth1, Kento Koketsu2, Akira Migita2, Christopher N Boddy3, Clay C C Wang1,4, Hiroki Oguri2 & Hideaki Oikawa2
Nonribosomal peptides (NRPs) are a class of microbial secondary metabolites that have a wide variety of medicinally important biological activities, such as antibiotic (vancomycin), immunosuppressive (cyclosporin A), antiviral (luzopeptin A) and antitumor (echinomycin and triostin A) activities1, 2. However, many microbes are not amenable to cultivation and require time-consuming empirical optimization of incubation conditions for mass production of desired secondary metabolites for clinical and commercial use3. Therefore, a fast, simple system for heterologous production of natural products is much desired. Here we show the first example of the de novo total biosynthesis of biologically active forms of heterologous NRPs in Escherichia coli. Our system can serve not only as an effective and flexible platform for large-scale preparation of natural products from simple carbon and nitrogen sources, but also as a general tool for detailed characterizations and rapid engineering of biosynthetic pathways for microbial syntheses of novel compounds and their analogs.
- Department of Pharmaceutical Sciences, University of Southern California, Los Angeles, California 90033, USA.
- Division of Chemistry, Graduate School of Science, Hokkaido University, Sapporo 060-0810, Japan.
- Department of Chemistry, Syracuse University, Syracuse, New York 13244-4100, USA.
- Department of Chemistry, University of Southern California, Los Angeles, California 90033, USA.
Correspondence to: Kenji Watanabe1 e-mail: kenjiwat@usc.edu
Correspondence to: Hideaki Oikawa2 e-mail: hoik@sci.hokudai.ac.jp
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