Engineering high value theraputic peptides from plastic waste

The Problem: Plastic is essential to modern society, driven primarily by its incredible versatility as a material coupled with its low production costs and energy requirement1. As a result, global production exceeds 330 million tons of oil-based plastics per annum and the enormity of the multi-tiered environmental plastic problem is now very apparent. Only 9% of plastic gets recycled and even then, only a limited number of times due to thermal degradation. The remaining plastic pollutes the environment or sits in landfill sites, where it can take up to 500 years to decompose, leaching toxic chemicals into the ground. Traditional plastics such as the polyester poly (ethylene terephthalate) (PET) are made from oil based raw materials. PET makes up almost one sixth of the world's annual plastic production of 311 million tons. Despite being one of the more commonly recycled plastics, only half is ever collected and recycled, considerably less actually ends up being reused.

The Solution: We propose to upcycle polyesters into highly valuable therapeutic peptides, which are of considerable interest possessing several highly sought-after properties including protease resistance and rigid scaffolds that can be almost infinitely diversified. Their size and molecular complexity means that they can target protein-protein interactions, a task that current small molecule drugs struggle to achieve. The PhD project will target poly (ethylene terephthalate) (PET), the most abundant, mechanically recyclable polyester, produced at a market demand of circa 30 million tons per annum.

Hypothesis
The overarching hypothesis of this project is that plastic waste can act as a steppingstone to a circular plastics economy by creating high value chemical products.

Aim
The overall project aims are to engineer a host platform for the conversion of PET to high value peptides.

Objectives:
The primary objective being to develop a microbial cell factory capable of converting PET to peptides: the student will utilize a combination of gene knockouts/knock-ins coupled with overexpression of target enzymes to enable maximised PET degradation and the efficient conversion of the PET breakdown products, terephthalic acid (TPA) and ethylene glycol. Conventional liquid chromatography (LC)-mass spectrometry (MS)-based metabolomics and stable isotope-assisted metabolic pathway analysis methods, coupled with 13C flux will be utilised to predict in vivo enzyme reaction rates, unravelling metabolism, and providing exemplar kinetic data, allowing for the development of designer strain with improved plastic degradation and TPA conversion.