Biosynthesis of cobalamin (vitamin B12): a bacterial conundrum

Abstract

The biosynthesis of cobalamin (vitamin B12) is described, revealing how the concerted action of around 30 enzyme-mediated steps results in the synthesis of one of Nature's most structurally complex 'small molecules'. The plethora of genome sequences has meant that bacteria capable of cobalamin synthesis can be easily identified and their biosynthetic genes compared. Whereas only a few years ago cobalamin synthesis was thought to occur by one of two routes, there are apparently a number of variations on these two pathways, where the major differences seem to be concerned with the process of ring contraction. A comparison of what is currently known about these pathways is presented. Finally, the process of cobalt chelation is discussed and the structure/function of the cobalt chelatase associated with the oxygen-independent pathway (CbiK) is described.

The Structural Basis for Methylmalonic Aciduria

“…Animals require cobalamin but must rely on dietary sources, and it is believed that plants and fungi neither synthesize nor use cobalamin (1,3). A characteristic that distinguishes cobalamin from all other vitamins is that only certain bacteria and archaea possess the ability for its de novo synthesis (3,4).…”

“…Cobalamin itself comprises a central corrin ring that provides four ligands for a hexacoordinated cobalt ion (3,4). The conversion of cobalamin to AdoCbl and MeCbl involves the reduction of the cobalt ion from a Co(III) oxidation state to Co(I) and then the addition of the functional ligand (2,10).…”

Identification of the gene responsible for the cblA complementation group of vitamin B 12 -responsive methylmalonic acidemia based on analysis of prokaryotic gene arrangements

“…V itamin B 12 (cobalamin, Cbl) is one of the most complex vitamins found in nature (1). It acts as a coenzyme in variety of molecular rearrangements to generate oxidizable substrates.…”

Vitamin B 12 - Structure, Biosynthesis , Functions, and Methods of Determination

“…Obie te formy są bardzo niestabilne w obecności światła, co objawia się zmianą widma absorpcji oraz utratą aktywności koenzymatycznej [3]. Trwałą formą witaminy B 12 , produkowaną na skalę przemysłową i niewystępującą w przyrodzie, jest cyjanokobalamina (CNCbl) [69]. Jest ona stabilna w obecności tlenu, a w formie suchej jest także odporna na działanie wysokiej temperatury (100 ºC).…”

“…Witamina B 12 jest jedyną witaminą, której synteza możliwa jest jedynie w komórkach bakteryjnych i archebakteriach [49,72]. Do biosyntezy witaminy B 12 de novo zaangażowanych jest ponad 30 genów, które stanowią ok. 1 % typowego genomu bakteryjnego [77] i obecne są u 1/3 zsekwencjonowanych genomów bakterii [69]. Obecnie znane są dwa odmienne szlaki biosyntezy kobalaminy w naturze.…”