A genetically modified bacterial production system for making yersiniabactin (Ybt) and novel analogs thereof, all of which are useful for the binding and removal of metals.
Given the costs associated with the loss of certain metals and the need to meet strict EPA regulations for residual metal content in manufacturing waste streams, there is great interest in solutions for their removal and recovery. Current technologies aimed at recovering these metals suffer from technical and economic limitations that often render their use unprofitable. Yersiniabactin (Ybt) is a natural product that enables sequestration of iron by Yersinia pestis, the bacterial pathogen that produces it to counter the effects of nutritional immunity by the host. Aside from iron, Ybt is known to bind other metals, including nickel and copper. The metal binding capabilities of Ybt offer the possibility of widespread applications related to selective metal removal and recovery, but complexities and dangers associated with its native production in Y. pestis prohibit use of Ybt from becoming a commercial reality.
The metabolic production of Ybt has been genetically engineered into an industrially relevant, non-pathogenic bacteria, thus enabling a scalable, cost effective means of production while simultaneously overcoming the hurdles presented by its native production. When immobilized on a resin, Ybt (generally referred to as XAD-Ybt) demonstrated superior performance when compared to commercially available metal scavengers such as QuadraPure TU®, regardless of whether it was used alone or in combination with a pretreatment column. When using the latter methodology, the combination of a pretreatment column and a column containing XAD-Ybt scavengers removed between 95 to 100% of copper. In addition to superior metal scavenging ability, the metal bound to XAD-Ybt scavengers can be recovered through a variety of cost-effective approaches, allowing the metal to be recycled and the scavengers to be reused with little, if any, degradation in performance. To date, Ybt has been shown to bind iron, gallium, nickel, copper, chromium, zinc, cobalt, palladium, magnesium and aluminum.
Appl Environ Microbiol. 2015 Aug; 81(16): 5290-5298
Biotechnol. Prog., 2017 33:1548-1554
This heterologous production system enables safe and ready access to commercially scalable quantities of Ybt. Further, variations of this system offer the ability to synthesize novel Ybt analogs, each of which possess unique metal binding affinities and selectivities.
• Removal and recovery of select metals
• Water treatment
• Rust removal
• Treatment of clinical conditions involving excess metal deposition (e.g. Wilson’s disease)
• Screening platform to identify siderophore inhibitors
Intellectual Property Summary:
US Non-Provisional Patent Application 15/559,604 (20180065940) filed March 21, 2016.
Stage of Development: Prototype demonstration.
Licensing Status: Available for licensing and collaboration.