Illuminating the black box of B 12 biosynthesis

Abstract

Tetrapyrroles are nearly ubiquitous in nature as participants in a wide variety of biological reactions that are central to life, such as electron transfer, gas binding, and one-carbon metabolism (1, 2). Because of their diverse colors—for example the greens of plant chlorophylls, reds of blood, and blues and browns of avian eggs—tetrapyrroles have been called the “pigments of life.” The chemical diversity of cyclic tetrapyrroles owes much to their ability to coordinate a variety of redox active metals in a fashion that allows for fine-tuning of midpoint potentials, increasing or decreasing reactivity of the metal center, and providing protection against undesirable side reactions. One finds magnesium in chlorophyll, iron in hemes, nickel in factor F430, and cobalt in cyano-cobalamin (vitamin B12) (Fig. 1). Although hemes and chlorophyls are synthesized by both prokaryotes and eukaryotes, factor F430, which is involved in methanogenesis, is produced only by some archae, and cobalamin synthesis is found only in bacteria and archae. With regard to cobalamin, it has long been known that two distinct pathways exist for its biosynthesis, one aerobic and the other anaerobic. Whereas the genes required for both aerobic and anaerobic synthesis have been known, the actual mechanism for synthesis via the anaerobic pathway has remained a large “black box” in what is one of the longest known biosynthetic pathways. However, the contents of this box have now been identified and characterized, thanks to an elegant study that can properly be called a tour de force by Moore et al. at the University of Kent (3). Fig. 1. The family of tetrapyrroles originating from uroporphyrinogen III. The central metal atom is colored to represent the color of the metallo-tetrapyrrole. … [↵][1]1E-mail: hdailey{at}uga.edu. [1]: #xref-corresp-1-1