Projects in our lab

Current projects in the lab focus on exploring interactions that exists within biological systems. We are using microbial vitamin biosynthesis and utilization pathways to probe enzyme-substrate, enzyme-enzyme and microbe-microbe interactions.

Unlocking the complexity and immense interconnectedness of the scientific mechanisms which dictate the properties and processes of the natural world is a major goal of the ABH lab. To this end, we seek to acquire a detailed understanding of many systems and how these various systems function together to generate the observations and measurements from our experimentation. Have a look at some of our projects below.

Mechanistic enzymology of the anaerobic biosynthesis of the lower ligand of vitamin B12

The anaerobic biosynthesis of Vitamin B12 involves the bza operon, which contains three methyltransferases BzaC, BzaD, and BzaE, each with a unique function. We are currently exploring the mechanisms of each of these three enzymes which have distinct domains and co-factor requirements. Additionally, the mechanistic enzymology of BzaD and BzaE is unprecedented in biological chemistry.

Cross-feeding of Vitamin B1 and intermediates in its biosynthetic pathways in synthetic microbial communities

Many ecosystems are composed of consortia of microbes, many of which are auxotrophic for the synthesis of essential biomolecules, that is, they are unable to synthesize them. Vitamins such as B1, B7 and B12 are amongst the repertoire of such critical metabolites that often get exchanged in the gut and marine microbial communities.

The modular nature of the vitamin B1 (thiamin) biosynthesis allows for such auxotrophies to be commonly observed in nature. So far, the exchange of the key intermediates in this pathway has not been studied systematically. We thus set up synthetic co-cultures of the thiamin biosynthesis mutants of Escherichia coli to investigate the exchange of B1 biosynthesis intermediates. We also look at the changing co-culture dynamics, in terms of the microbes and the concentrations of the intermediates involved.

Investigating the molecular basis of nucleobase specificity in nucleotide-utilizing enzymes

Phosphorylation reactions in biological chemistry typically utilize a nucleotide triphosphate. For example, ATP is a commonly used substrate for kinase enzymes. However, the phosphorylation reaction involves only the use of the triphosphate part of the molecule - the role of the specific nucleobase, adenine in this case, is not apparent. Additionally, vitamins such as SAM, flavin adenine dinucleotide, and Coenzyme A contain the nucleobase adenine. We are currently investigating the specificity aspect of the nucleobase in enzyme catalysis and biological chemistry.