Michi Taga

My lab is interested in understanding how vitamin B₁₂ and B₁₂-like compounds are produced and how these molecules function at an enzymatic, organismal, and community level.

Vitamin B₁₂ (cobalamin) is an essential component of animal diets. B₁₂ functions as a cofactor for two enzymatic reactions in humans and many additional reactions in bacteria. Although the utilization of B₁₂ as a cofactor is widespread, B₁₂ biosynthesis is limited exclusively to certain prokaryotes. We seek to understand the major unknown component of the B₁₂ biosynthetic pathway, the synthesis of the lower ligand of B₁₂, DMB. Additionally, we are interested in the diversity of B₁₂-like compounds and their utilization by both B₁₂-producing bacteria and other organisms in their communities.

We are currently investigating the following three areas related to B₁₂ biosynthesis and function:

We have discovered in Sinorhizobium meliloti the remarkable “flavin destructase” enzyme, BluB, which catalyzes a previously unknown step in the B₁₂ biosynthetic pathway, the synthesis of DMB. BluB catalyzes the oxygen-dependent fragmentation of flavin mononucleotide (FMN) to form DMB, and thus is the only enzyme known to destroy a flavin cofactor in order to produce another cofactor, B₁₂. We are analyzing BluB’s mechanism by combining genetic and biochemical methods. Additionally, we are investigating the DMB biosynthetic pathway employed by anaerobic bacteria by a combined bioinformatic, genetic, and biochemical strategy.

S. meliloti is a Gram-negative bacterium that exists in two distinct lifestyles. It is often found free-living in soil, where it competes with many other soil bacteria for a limited supply of nutrients. S. meliloti can also exist in a symbiotic relationship with certain leguminous plants (Fig. 2). Within the plant host, S. meliloti converts atmospheric nitrogen to ammonia, a process called nitrogen fixation. In S. meliloti, the B₁₂-dependent ribonucleotide reductase enzyme, which is required for DNA synthesis, is essential for the development of the bacteria into mature nitrogen-fixing bacteroids. We are investigating the physiological basis of the B₁₂ requirement in intracellular survival of S. meliloti within its plant host.