Cofactor biosynthesis--still yielding fascinating new biological chemistry

Abstract

This mini review covers recent advances in the mechanistic enzymology of cofactor biosynthesis.

Figure 1

Thiamin phosphate 3 is biosynthesized by coupling the thiazole 1 with the pyrimidine 2.

Figure 2

Mechanistic proposal for the formation of the thiamin thiazole 1 in bacteria. ThiS represents the sulfide carrier protein.

Figure 3

Mechanistic proposal for the ThiH-catalyzed formation of glycine imine (14) under anaerobic conditions.

Figure 4

Labeling studies that map out the complex conversion of aminoimidazole ribotide to the thiamin pyrimidine.

Figure 5

Mechanistic proposal for the formation of the thiamin thiazole (41) in S. cerevisiae.

Figure 6

The pyrimidine moiety of thiamin in S. cerevisiae is formed by a remarkable reaction sequence in which the histidine atoms labeled in blue and the PLP atoms labeled in red are incorporated into the pyrimidine 44.

Figure 7

A new thiamin salvage pathway for the recycling of the pyrimidine of thiazole-degraded thiamin.

Figure 8

MoaA and MoaC catalyze the formation of Precursor Z (49) on the molybdopterin biosynthetic pathway.

Figure 9

A mechanistic proposal for the formation of PLP (43). Pdx1 represents the pyridoxal phosphate synthase.

Figure 10

Shown is the major bacterial pathway for the formation of the quinolinic acid (68) precursor to NAD 28.

Figure 11

Shown is the mechanistic proposal for the formation of quinolinic acid 68 from hydroxyanthranilate (69).

Figure 12

Mechanistic proposal for the oxidative decarboxylation of coproporphyrinogen III (74) to protoporphyrinogen IX (75).

Figure 13

Mechanistic proposal for the oxidation of FMN 79 to dimethylbenzimidazole 87.