Unlocking the potential of non-model bacteria : a cross-bacterial gene expression toolbox

Microbial cell factories have great potential in the field of industrial biotechnology to produce existing and new-to-nature compounds in a sustainable manner. This capability will be essential to alleviate some of society’s main economic, social and environmental challenges and lay the foundations for a knowledge-based, circular and bio-based economy. Despite this potential, the development of commercially viable microbial cell factories is currently limited by high costs and long time-to-market relative to other production routes. One cause is an over-reliance on model organisms such as E. coli, which are often not optimal for harsh industrial growth conditions, substrate and application, causing problems such as toxic build-up of metabolites, metabolic burdens and inefficient use of resources. Whilst the exploitation of a wide range of bacterial hosts, from extremophiles to native producers, can help us to realise the full potential of industrial biotechnology, the lack of extensive and standardised genetic parts and tools to control gene expression in alternative bacterial hosts is a major bottleneck. A genetic engineering toolbox that can reliably operate in any chasis has incredible potential to remove this limitation by allowing us to exploit any bacterial species without the requirement to develop specific tools for each host. This research aims to develop and characterise a cross-bacterial, orthogonal and tuneable gene expression system, allowing predictable engineering in non-model bacterial hosts. Such a genetic toolbox is a key enabling technology in the sustainable production of enzymes, pharmaceuticals, chemical building blocks, fuels and foods, thereby facilitating the transition to a bio-based economy.Microbial cell factories have great potential in the field of industrial biotechnology to produce existing and new-to-nature compounds in a sustainable manner. This capability will be essential to alleviate some of society’s main economic, social and environmental challenges and lay the foundations for a knowledge-based, circular and bio-based economy. Despite this potential, the development of commercially viable microbial cell factories is currently limited by high costs and long time-to-market relative to other production routes. One cause is an over-reliance on model organisms such as E. coli, which are often not optimal for harsh industrial growth conditions, substrate and application, causing problems such as toxic build-up of metabolites, metabolic burdens and inefficient use of resources. Whilst the exploitation of a wide range of bacterial hosts, from extremophiles to native producers, can help us to realise the full potential of industrial biotechnology, the lack of extensive and standardised genetic parts and tools to control gene expression in alternative bacterial hosts is a major bottleneck. A genetic engineering toolbox that can reliably operate in any chasis has incredible potential to remove this limitation by allowing us to exploit any bacterial species without the requirement to develop specific tools for each host. This research aims to develop and characterise a cross-bacterial, orthogonal and tuneable gene expression system, allowing predictable engineering in non-model bacterial hosts. Such a genetic toolbox is a key enabling technology in the sustainable production of enzymes, pharmaceuticals, chemical building blocks, fuels and foods, thereby facilitating the transition to a bio-based economy.C