Amy C. Rosenzweig Weinberg Family Distinguished Professor of Life Sciences, Molecular Biosciences, Chemistry

Research Interests

Structural biology and bioinorganic chemistry, metal uptake and transport, oxygen activation by metalloenzymes, biological methane oxidation, membrane proteins, natural products biosynthesis

Current research in our laboratory focuses on methanotrophic bacteria, organisms that oxidize methane to methanol in the first step of their metabolic pathway. Methanotrophs have attracted much attention as a means of mitigating methane emissions and for their potential applications in bioconversion of methane to fuels and chemicals. Whereas current catalysts that can selectively activate the 105 kcal mol-1 C-H bond in methane require high temperatures and pressures, methanotrophs perform this chemistry under ambient conditions using methane monooxygenase (MMO) enzymes. The predominant MMO in nature, particulate MMO (pMMO), is a three-subunit, integral membrane protein. Despite extensive research and the availability of multiple crystal structures, the active site structure and chemical mechanism of pMMO remain a major unsolved problem in bioinorganic chemistry. Current efforts in the laboratory are directed at elucidating the atomic details of the copper active site, understanding the mechanisms of dioxygen activation and methane oxidation, including how substrates, products, electrons, and protons access the active site, and probing the function of pMMO within the larger context of methanotroph physiology.

In a related project, we are studying a natural product first identified in methanotrophs called methanobactin (Mbn). Mbn, a ribosomally-produced post-translationally modified natural product (RiPP) that binds copper with high affinity, is a potential copper chelating drug for human disorders of copper metabolism as well as a starting point for developing new metal-chelating drugs and antibiotics. All Mbns characterized thus far bind Cu(I) with two nitrogen-containing heterocycles and two adjacent thioamide groups. The biosynthetic and transport machinery for Mbn is encoded by operons, which are also found in a range of non-methanotrophic bacteria, including gram-positive pathogens, suggesting a broader role in and perhaps beyond copper acquisition. Current efforts in the laboratory are focused on discovering new Mbns and related natural products, characterizing the proteins involved in Mbn export and import, and unraveling the mechanisms of its biosynthesis. 

Selected Publications

A tale of two methane monooxygenasesRoss MO and Rosenzweig AC. Journal of Biological Inorganic Chemistry. 2017 April;22(2-3):307-319.

Methanobactins: from genome to function. Dassama LMK, Kenney GE, and Rosenzweig AC. Metallomics. 2017 January 1;9(1):7-20.

Methanobactin transport machinery. Dassama LMK, Kenney GE, Ro SY, Zielazinski EL, and Rosenzweig AC. PNAS. 2016 November 15;113(46):13027-13032.

Methane-Oxidizing Enzymes: An Upstream Problem in Biological Gas-to-Liquids Conversion. Lawton TJ and Rosenzweig AC. Journal of the American Chemical Society. 2016 August 3;138(30):9327-9340.

Printable enzyme-embedded materials for methane to methanol conversion. Blanchette CD, Knipe JM, Stolaroff JK, DeOtte JR, Oakdale JS, Maiti A, Lenhardt JM, Sirajuddin S, Rosenzweig AC, and Baker SE. Nature Communications. 2016 June 15;7:11900.

View all publications by Amy C. Rosenzweig listed in the National Library of Medicine (PubMed). Current and former IBiS students in blue.