Enzymatic synthesis and structure of precorrin-3, a trimethyldipyrrocorphin intermediate in vitamin B12 biosynthesis

• Published in: Biochemistry (Easton) Vol. 31; no. 2; pp. 603 - 609
• Main Authors: WARREN, M. J, ROESSNER, C. A, OZAKI, S.-I, STOLOWICH, N. J, SANTANDER, P. J, SCOTT, A. I
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 21.01.1992
• Subjects: Analytical, structural and metabolic biochemistry; Biological and medical sciences; Coenzymes, vitamins; Escherichia coli - genetics; Fundamental and applied biological sciences. Psychology; Genetic Vectors; Hydroxymethylbilane Synthase - chemistry; Magnetic Resonance Spectroscopy; Methyltransferases - chemistry; Other biological molecules; Porphobilinogen - chemistry; Porphobilinogen Synthase - chemistry; Pseudomonas - genetics; Uroporphyrinogen III Synthetase - chemistry; Uroporphyrins - biosynthesis; Uroporphyrins - chemistry; Vitamin B 12 - biosynthesis; Vitamin B 12 - genetics; Metabolic intermediate; Enzymatic synthesis; HPLC chromatography; NMR spectrometry; Molecular structure; Corrin
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi00117a043

The trimethylated intermediate of vitamin B12 (corrin) biosynthesis, precorrin-3, was produced from various 13C-enriched isotopomers of 5-aminolevulinic acid (ALA), using a multiple-enzyme system containing ALA dehydratase, porphobilinogen deaminase, uro'gen III synthetase, and the S-adenosyl-L-methionine-(SAM)-dependent uro'gen III methyltransferase (M-1) and precorrin-2 methyltransferase (M-2) in the presence of [13C]SAM. Structural analysis of the resulting product, precorrin-3, reveals a close similarity to precorrin-2 but with several subtle differences in the conjugated array of C = C and C = N bonds which reflect the presence of the new C-methyl group at C20 and its influence on the electronic distribution in the dipyrrocorphin chromophore. The implications of this structure for corrin biosynthesis are discussed.