The Warren research group interests envelop areas of chemistry, biology and history.
Our aim is to understand how nature is able to mediate the construction of complex small molecules such as vitamin B12 and then to utilise this knowledge for useful purposes.
Our research has led to the elucidation of how molecules such as heme, heme d1, coenzyme F430 and cobalamin (vitamin B12) are made in bacterial cells. This knowledge is being utilised to enhance B12 production through recombinant bacterial strains. Our ability to make fluorescent versions of vitamin B12 has shown that certain plants are able to absorb B12 from the soil and this approach is being used to see if B12 -enriched plants can be used to enhance the diets of vegans and vegetarians.
In complex microbial communities the ability to make nutrients such as B12 provides specific bacteria with a strong selective advantage, allowing them to share a valuable resource that can be exchanged for other key commodities. Similarly, metabolosomes (bacterial microcompartments) provide specific bacteria with the ability to breakdown substrates via toxic intermediates. We aim to understand how and when these properties are utilised within the gastrointestinal tract.
Our work on metabolosomes has shown that these organelles can be used to accumulate excess phosphate. Our engineering approach has also shown that the shell components of metabolosomes can be used as cellular scaffolds for in cell protein design.
We utilise recombinant DNA and synthetic biology approaches to probe biosynthetic and metabolic pathways through reconstruction. For instance, we have cloned the whole cobalamin (vitamin B12) pathway in E. coli, an organism that does not possess the ability to make this molecule de novo. In some doing this approach also provides us with ready access to a whole range of cobalamin precursors and analogues. Similarly, with metabolosomes we are able to reconstruct recombinant organelles within E. coli and learn about how these compartments are made and how cargo is internalised within them.