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SoCoBio (Universities of Southampton, Kent, Sussex, Portsmouth and NIAB EMR)

A dual approach to the Biofortification of Lettuce and Pea with Vitamin B12 The following proposal aims to address Vitamin B12 deficiencies within the population by biofortifying crops such as pea and lettuce

Dr Andrew Simkin (PI)
Dr Eleftheria Stavridou (co-I)

University of Kent
Prof Martin Warren (PI)

Project Summary

The work will be broken down into three packages representing short (WP1), medium (WP2) and long-term (WP3) approaches to boosting B12 availability in green tissue for human consumption.

B12 is made exclusively by a small group of prokaryotes (bacteria and archaea)1. Some of these bacteria are found in the flora of ruminant mammals where they proliferate in the stomach and continue to form B12. This source of B12 therefor accumulates in animal product including meat, eggs, milk and is the key dietary source of B12 in the population. B12 is absent from fruits and vegetables2.
B12 is an essential nutrient for animals and B12 deficiency can result in a range of symptoms including depression, loss of memory (reduced cognitive performance), fatigue, lethargy and headaches and in some people mania and psychosis3,4,5. Research has shown that as much as 40% of the world’s population are deficient in B12.
Biofortification of plants via feeding mechanisms has demonstrated that Lepidium sativum (garden cress) can take up B12 if grown in B12 enriched media, where it accumulates in the vacuole of the cotyledons6,7.

Work Packages
WP1 Will study feeding of B12 to pea and lettuce in Aquaponics systems to evaluate the mechanism of uptake and bioavailability.- Novel systems of cultivation such as aeroponics and vertical farming will be evaluated (feeding regimes = feeding product).

WP2 Will express bacterial B12 binding proteins in pea and lettuce to improve the stockage and bioavailability. Conduct feeding experiments (as WP1). 8,9

WP3 As a first step in engineering Vitamin B12 biosynthesis into lettuce, we will look to produce the first 9 steps of the aerobic pathway for cobalamin biosynthesis in the lettuce plastid, where the B12 pathway can syphon from the haem and chlorophyll pathways. This will involve the cloning of cobA-I-G-J-M-F-K-L-H genes and will result in the production of a stable intermediate called hydrogenobyrinic acid.

1. Roth et al. Cobalamin (coenzyme B12): Synthesis and biological significance. Annual Review of Microbiology 1996, 50, 137-181.
2. Watanaba F. Vitamin b12 sources and bioavailability. Experimental Biology and Medicine 2007, 232, 1266-1274.
3. Masalha R et al. Cobalamin-responsive psychosis as the sole manifestation of vitamin b12 deficiency. Israel Medical Association Journal 2001, 9, 701-703.
4. Biemans, E et al. Cobalamin status and its relation with depression, cognition and neuropathy in patients with type 2 diabetes mellitus using metformin. Acta Diabetologica 2015, 52, 383-393.
5. Pruthi and Tefferi, A. Pernicious anemia revisited. Mayo Clinic Proceedings 1994, 69, 144-150.
6. Warren et al. The biosynthesis of adenosylcobalamin (vitamin B12). Natural Product Reports 2002, 19, 390-412.
7. Lawrence et al. Construction of fluorescent analogs to follow the uptake and distribution of cobalamin (vitamin B12) in bacteria, worms, and plants. Cell Chem Biol 2018, 25, 941-951 e946.
8. Grant et al. Transformation of peas (Pisum sativum L.) using immature cotyledons. Plant Cell Rep 1995, 15, 254-258.
9. Dan et al. Genetic Transformation of Lettuce. A review. A J of Biotech 2014, 13, 1686-1693.