Total biosynthesis of antitumor nonribosomal peptides in Escherichia coli.
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) activities. 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 use. 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.
Watanabe
Kenji
K
Department of Pharmaceutical Sciences, University of Southern California, Los Angeles, California 90033, USA.
Hotta
Kinya
K
Praseuth
Alex P
AP
Koketsu
Kento
K
Migita
Akira
A
Boddy
Christopher N
CN
Wang
Clay C C
CC
Oguri
Hiroki
H
Oikawa
Hideaki
H
D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism*; D001709:Biotechnology / Q000379:methods; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000235:genetics; D005818:Genetic Engineering / Q000379:methods; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010452:Peptide Biosynthesis; D010456:Peptides, Cyclic / Q000096:biosynthesis* / Q000737:chemistry; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D016326:Extracellular Matrix Proteins; D010456:Peptides, Cyclic