Professor Jonathan Caranto

Professor Jonathan Caranto
Department of Chemistry
University of Central Florida
Printable Abstract

Metalloenzyme-catalyzed oxidations of nitric oxide in biosynthesis and nitrosative stress protection

While nitric oxide (NO) is often regarded as toxic, the emerging evidence suggests its productive biological functions are as diverse as those of O2. NO biochemistries are involved in cell signaling, bioenergetics, natural product biosynthesis, and nitrosative stress protection. While mechanisms for reductive NO biochemistries are well studied, less is known about the mechanisms of oxidative NO biochemistries, which is one focus of our lab.

This presentation will discuss our latest work on a cytochrome P450 (CYP) homolog, called TxtE, which catalyzes an NO-dependent nitration of L-tryptophan (Trp) to form 4-nitrotryptophan (4-NO2- Trp). This enzyme produces 4-NO2-Trp as a biosynthetic precursor of thaxtomin A—a virulence factor of the potato disease scab. Studies of a Thr250 TxtE mutant suggest that the mutant has a disrupted water network that also eliminates nitration activity. Based on these results, it is proposed that proton transfer is critical for TxtE activity. 

In addition, our studies of a hemerythrin-like protein found in pathogenic Mycobacteria (mycoHLP) will be discussed. We previously showed that these mycoHLPs exhibit NO peroxidase activities and other NO oxidations typically observed by heme proteins. The observed NO reactivities suggest mycoHLPs function as nitrosative stress protection enzymes. These mycoHLPs contain a Tyr-ligated non-heme diiron site, which has not been observed in other HLPs. Mutants of this Tyr ligand suggest this ligand is critical for activity. Furthermore, the results suggest that a mixed-valent (FeII-FeIII) species is an intermediate of the NO peroxidase pathway.

Jonathan Caranto

Dr. Jonathan Caranto is as assistant professor in the Department of Chemistry at the University of Central Florida. He is the PI of NOx Nation, a lab that discovers and studies mechanisms of nitrogen biochemistries. Specifically, his lab studies the mechanisms of nitric oxide-dependent metalloenzymes and the bacterial biosynthesis and biodegradation of nitramine natural products. His lab also engineers enzymes to support biocatalytic approaches to generate and bioremediate nitrated compounds, including high- energy compounds. Dr. Caranto obtained his PhD at the University of Texas at San Antonio with Prof. Donald Kurtz and served as a post- doc at Cornell University with Prof. Kyle Lancaster.

Hosted by Professor Ambika Bhagi-Damodaran