Durham University

Metal cofactors (eg iron-heme, magnesium-chlorophyll, cobalt-vitamin B₁₂) are some of the most important molecules produced in nature. Crucially, metallocofactors must acquire the correct metal to be functional. How organisms achieve metal specificity is only partially understood. This research will characterise the cobalt delivery pathway for vitamin B₁₂.

B₁₂ is one of only a few essential nutrients missing from a vegan diet, key to a sustainable future food supply. B₁₂ is the most expensive vitamin on the market and unavailable to many (particularly in developing nations) who need it. To address this problem, there is considerable interest in engineering industrially appropriate bacteria (E. coli) to produce B₁₂: such systems could be widely employed in future to make supplements affordable in low-income areas. However, B₁₂ contains a metal (cobalt) crucial for function and the metalation step of B₁₂ biosynthesis can be a problem for manufacture.

I have recently been studying the metal-binding properties of the uncharacterised B₁₂ biosynthesis protein CobW and have uncovered compelling evidence that this protein acquires cobalt for vitamin B₁₂ in bacterial cells. I have proposed a mechanism which explains how CobW obtains cobalt from the cellular milieu and delivers this metal to B₁₂ during biosynthesis but also predicts that CobW will struggle to become correctly metallated under certain bacterial growth conditions. This may be a root cause stalling B₁₂ metalation and limiting high B₁₂ yields.

This research will use a variety of chemical and biological techniques to discover:

1. How CobW confers specificity for the correct metal (cobalt) and the correct destination (B₁₂).
2. Under which growth conditions this specificity is compromised (ie can CobW end up with the wrong metal?) and if this inhibits B₁₂
3. Ways to use this understanding to enhance correct metalation of B₁₂.

This work will both contribute fundamental scientific understanding of how organisms get the right metal to the right place inside a cell and, through interaction with industrial partners via the Durham-led BBSRC-NIBB (https://bbsrc.ukri.org/news/industrial-biotechnology/2018/181108-pr-11m-to-fund-industrial-biotechnology-and-bioenergy-networks-announced/), support the development of high-yielding (affordable) B₁₂ production systems for sustainable global nutrition.