Research Group Overview

Dr. Biswarup Mukhopadhyay's research group studies the biochemical mechanisms used by microorganisms to survive under extreme conditions. Research in the laboratory focuses on the physiology, enzymology and evolutionary biology of methanogenic archaea, mycobacterial metabolism and tuberculosis, and microbiological conversion of coal to methane in deep subsurface coalbeds. 

Methanocaldococcus jannaschii is a methane-producing organism found in submarine hydrothermal vents.  The Mukhopadhyay research group has discovered that M. jannaschii possesses a new type of enzyme, a sulfite reductase, which represents an ancient detoxification system.  This is the first time methane production and sulfite reduction have been shown not to be mutually exclusive processes.  M. jannaschii can carry out both processes because it contains a system to detoxify the otherwise toxic sulfite.  It is possible that at one time methanogenesis and sulfate reduction existed in one organism, which performed both methanogenesis and sulfate-dependent anaerobic oxidation of methane.

Mycobacterial metabolism and tuberculosis: Coenzyme F₄₂₀, a deazaflavin that is present in every methanogenic archaea and rare in bacteria, is found in every mycobacteria. Purwantini and Mukhopadhyay are investigating the role of this coenzyme in mycobacteria.  Purwantini and colleagues have shown that the mycobacteria carry an unusual glucose-6-phosphate dehydrogenase (G6PD) that reduces F₄₂₀ to F₄₂₀H₂;  previously known G6PDs utilize NAD or NADP and not F420.  Recently, Purwantini and Mukhopadhyay have shown that the F₄₂₀H₂ generated by the unusual G6PD (called Fgd) could help Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), to combat nitrosative attack by the macrophages and thereby to cause tuberculosis.   Further focus is on elucidating the role of F₄₂₀ in the synthesis of mycobacterial cell and the use this information to identify cellular targets for the development of therapeutics for TB.  Also, in collaboration with the Johns Hopkins University, Rotinsulu Pulmonary Hospital (Bandung, Indonesia), and Institut Teknolgi (Bandung, Indonesia) they are analyzing the genomic and immunological characteristics of clinical isolates of M. tuberculosis with the goal of developing diagnostics, vaccines and therapeutics for tuberculosis.

The Mukhopadhyay research group is also exploring the use of microorganisms to convert coal to methane and to reduce the risk of methane-induced mine explosion. This work is being carried out in collaboration with the Altuda Energy Corporation in San Antonio, Texas.

Studies of human phosphoenolpyruvate carboxykinase and an archaeal-type phosphoenolpyruvate carboxylase are allowing new avenues to be explored for designing drugs for treating type 2 diabetes and infections caused by Clostridium perfringens as well as improving CO₂ fixation efficiencies in plants.

Current laboratory members:

Past laboratory members:

Leader: Biswarup Mukhopadhyay