Journal
BIOCHEMISTRY
Volume 60, Issue 9, Pages 699-710Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.biochem.0c00950
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Funding
- National Institute of General Medical Sciences [R01GM124203]
- University of Georgia
- National Science Foundation Major Research Instrumentation (MRI) program in the Division of Chemistry [CHE-1827968]
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In response to increasing antibiotic resistance and growing recognition of the human microbiome, new therapeutic targets need to be identified. This study investigated the unique metabolic pathways of Vibrio cholerae, particularly the catalytic role of HutW in the anaerobic opening of the porphyrin ring of heme.
Increasing antibiotic resistance, and a growing recognition of the importance of the human microbiome, demand that new therapeutic targets be identified. Characterization of metabolic pathways that are unique to enteric pathogens represents a promising approach. Iron is often the rate-limiting factor for growth, and Vibrio cholerae, the causative agent of cholera, has been shown to contain numerous genes that function in the acquisition of iron from the environment. Included in this arsenal of genes are operons dedicated to obtaining iron from heme and heme-containing proteins. Given the persistence of cholera, an important outstanding question is whether V. cholerae is capable of anaerobic heme degradation as was recently reported for enterohemorrhagic Escherichia coli O157:H7. In this work, we demonstrate that HutW from V. cholerae is a radical S-adenosylmethionine methyl transferase involved in the anaerobic opening of the porphyrin ring of heme. However, in contrast to the enzyme ChuW, found in enterohemorrhagic E. coli O157:H7, there are notable differences in the mechanism and products of the HutW reaction. Of particular interest are data that demonstrate HutW will catalyze ring opening as well as tetrapyrrole reduction and can utilize reduced nicotinamide adenine dinucleotide phosphate as an electron source. The biochemical and biophysical properties of HutW are presented, and the evolutionary implications are discussed.
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