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Consolidated plasmid Design for Stabilized Heterologous Production of the complex natural product Siderophore Yersiniabactin
Author(s) -
Qi Ruiquan,
Swayambhu Girish,
Bruno Michael,
Zhang Guojian,
Pfeifer Blaine A.
Publication year - 2020
Publication title -
biotechnology progress
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.572
H-Index - 129
eISSN - 1520-6033
pISSN - 8756-7938
DOI - 10.1002/btpr.3103
Subject(s) - yersinia pestis , siderophore , polyketide , nonribosomal peptide , biology , plasmid , heterologous , microbiology and biotechnology , escherichia coli , biosynthesis , bacteria , genetics , gene , virulence
Yersiniabactin (Ybt) is a hybrid polyketide‐nonribosomal complex natural product also known as a siderophore for its iron chelation properties. The native producer of Ybt, Yersinia pestis , is a priority pathogen responsible for the plague in which the siderophore properties of Ybt are used to sequester iron and other metal species upon host infection. Alternatively, the high metal binding properties of Ybt enable a plethora of potentially valuable applications benefiting from metal remediation and/or recovery. For these applications, a surrogate production source is highly preferred relative to the pathogenic native host. In this work, we present a modification to the heterologous Escherichia coli production system established for Ybt biosynthesis. In particular, the multiple plasmids originally used to express the genetic pathway required for Ybt biosynthesis were consolidated to a single, copy‐amplifiable plasmid. In so doing, plasmid stability was improved from ~30% to ≥80% while production values maintained at 20–30% of the original system, which resulted in titers of 0.5–3 mg/L from shake flask vessels.