title: Biosynthesis of Yersiniabactin, a complex polyketide-nonribosomal peptide, using Escherichia coli as a heterologous host.
abstract: 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.
authors: Chemical Engineering, Stanford University, Stanford, California 94305, USA.
authors: Blaine A
authors: BA
authors: Pfeifer
authors: Clay C C
authors: CC
authors: Wang
authors: Christopher T
authors: CT
authors: Walsh
authors: Chaitan
authors: C
authors: Khosla
mesh_terms: 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
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D033862:Iron-Binding Proteins; D033902:Periplasmic Binding Proteins; D010636:Phenols; D017262:Siderophores; D013844:Thiazoles; C104398:yersiniabactin