Characterising the cobalt delivery pathway for vitamin B12

Dr Tessa Young
Research Fellow 2019

Dr Tessa Young
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:

 

“This work will significantly advance fundamental understanding of how cells perform the (vital-to-life) task of distributing metals to their correct destinations inside cells. Such understanding could have wide-reaching applications in industrial biotechnology."
  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.