Synthetic biology engineering of the halophilic archaeon Haloferax mediterranei as a cell factory for tailor-made polyhydroxyalkanoates.

Given the negative environmental impact of the production and use
of petroleum-based plastics, focus is shifting towards more
sustainable alternatives, such as microbial production of
biodegradable plastics with as a promising example
polyhydroxyalkanoates (PHAs). Despite this promise,
commercialization of PHA production is still limited due to low yields
and high production costs. The observation of natural PHA
biosynthesis in the halophilic archaeon Haloferax mediterranei, which
grows optimally at a salt concentration of 20-25% (w/v) is very
interesting, not only because of the advantages of using a halophile
in a PHA bioproduction process, but also because of the evidence
that the copolymeric composition of the PHA produced by H.
mediterranei is tuneable on a genetic level thanks to paralogs of
copolymer-supplying enzymes (PhaC). However, a synthetic biology
approach has never been used in Haloarchaea to exploit this. In this
project, I aim to generate insights on the native regulation of PHA
biosynthesis, on substrate specificity of the paralogous PhaC
enzymes and to develop predictable expression element libraries for
H. mediterranei. In an iterative cycle, novel genetic circuits will be
screened for improved PHA production and/or altered copolymer
composition, opening up new application possibilities. This PhD
project will not only generate a cell factory for tuneable PHAcopolymer bioproduction but also enhance the synthetic biology
toolbox for work in H. mediterranei.