Journal Article

Biosynthesis of Vitamin B12: Structure of Precorrin-6x Octamethyl Ester

Blanche, Francis, Thibaut, Denis, Battersby, Alan R., Debussche, Laurent, Leeper, Finian J.

1990

Overview

13C-labeled precorrin-6x is biosynthesized by cell-free protein preparations from Pseudomonas denitrificans in separate experiments using δ-amino[5-13C]levulinic acid and the corresponding δ-amino[4-13C]- and δ-amino[3-13C]levulinic acid-labeled forms in conjunction with S-[methyl-13C]adenosylmethionine for the latter two experiments. These labeled precorrin-6x samples, as their octamethyl esters, are studied by a range of NMR techniques. In addition, nuclear Overhauser effect difference measurements are made on unlabeled precorrin-6x ester to determine connectivities. The structure 6a so established for precorrin-6x ester (i) confirms the results reported in the preceding paper that precorrin-6x has a ring-contracted macrocycle, still carries the C-12 acetate residue, and stands at the oxidation level of a dehydrocorrin; (ii) reveals the unexpected methylation at C-11 not C-12, leading to a structure with separated chromophores; and (iii) implies that methyl migration from C-11 to C-12 occurs when precorrin-6x is converted into hydrogenobyrinic acid. Proposals for the biosynthesis of the corrin macrocycle of hydrogenobyrinic acid and vitamin B12are made.

• Publisher: National Academy of Sciences of the United States of America,National Acad Sciences
• Subject: Acetates / Analytical, structural and metabolic biochemistry / Atoms / Biological and medical sciences / Biosynthesis / Cell-Free System / Chemical bonding / Chemical equilibrium / Coenzymes, vitamins / Esters / Fundamental and applied biological sciences. Psychology / Hydrogen / Magnetic Resonance Spectroscopy / Methylation / Molecular Structure / Other biological molecules / Overhauser effect / Pseudomonas - metabolism / Uroporphyrins - chemistry / Vitamin B 12 - biosynthesis / Vitamin B12