Biosynthesis of Yersiniabactin, a complex polyketide-nonribosomal peptide, using Escherichia coli as a heterologous host.
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.
Pfeifer
Blaine A
BA
Chemical Engineering, Stanford University, Stanford, California 94305, USA.
Wang
Clay C C
CC
Walsh
Christopher T
CT
Khosla
Chaitan
C
D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D001709:Biotechnology / Q000379:methods; D004926:Escherichia coli / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D005285:Fermentation; D033862:Iron-Binding Proteins; D013058:Mass Spectrometry; D033902:Periplasmic Binding Proteins; D010636:Phenols; D017262:Siderophores / Q000096:biosynthesis*; D013844:Thiazoles
D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D033862:Iron-Binding Proteins; D033902:Periplasmic Binding Proteins; D010636:Phenols; D017262:Siderophores; D013844:Thiazoles; C104398:yersiniabactin