Search for Novel Arsenic-Containing Antibiotics
Disciplines
Amino Acids, Peptides, and Proteins | Inorganic Chemicals | Medical Microbiology | Medical Toxicology | Other Chemicals and Drugs
Abstract (300 words maximum)
Arsenic, a widely recognized environmental toxin associated with various health risks, surprisingly exhibits potential applications in the realm of medicine. Antibiotics, crucial for combating infectious diseases, represent a cornerstone in healthcare. Recent research has shown a fascinating relationship between bacteria and arsenic, revealing that bacteria leverage environmental arsenic to synthesize unique antibiotics containing this element.
A noteworthy instance of this phenomenon is observed in arsinothricin, the sole known arsenic-containing antibiotic. This compound has showcased its effectiveness in addressing antibiotic-resistant pathogens while showing selectivity in sparing human cells. This revelation paves the way for new possibilities in antibiotic research and development. Our objective is to build upon this unique connection and delve into the discovery of additional arsenic-containing antibiotics. This endeavor holds the potential to broaden the spectrum of resources available for combating infectious diseases and tackling the growing challenge of antibiotic resistance.
The gene set (so-called biosynthetic gene cluster, or BGC) required for arsinothricin biosynthesis were used to search sequenced genome database, which let to the discovery of several prospective BGCs for arsenic-containing antibiotics. Among them, our target is those for arsenic-containing RiPPs (Ribosomally synthesized and Post-translationally modified Peptides), especially the one from Microbispora rosea. From our target RiPP BGC, we selected four genes, which we hypothesize are the minimum required to produce an arsenic-containing precursor of the encoded RiPP, and used them to transformed Escherichia coli using a two-plasmid system. Expression of the transformed genes in E. coli was analyzed using SDS-PAGE, however, some of the gene-encoded proteins were not properly expressed. To solve the expression issue, we are currently optimizing the condition. Given that arsenic-containing peptides have never been discovered in the nature, the discovery of arsenic-containing RiPP antibiotics will not only support our hypothesis but also have a big impact over the related fields.
Academic department under which the project should be listed
CSM - Molecular and Cellular Biology
Primary Investigator (PI) Name
Masafumi Yoshinaga
Search for Novel Arsenic-Containing Antibiotics
Arsenic, a widely recognized environmental toxin associated with various health risks, surprisingly exhibits potential applications in the realm of medicine. Antibiotics, crucial for combating infectious diseases, represent a cornerstone in healthcare. Recent research has shown a fascinating relationship between bacteria and arsenic, revealing that bacteria leverage environmental arsenic to synthesize unique antibiotics containing this element.
A noteworthy instance of this phenomenon is observed in arsinothricin, the sole known arsenic-containing antibiotic. This compound has showcased its effectiveness in addressing antibiotic-resistant pathogens while showing selectivity in sparing human cells. This revelation paves the way for new possibilities in antibiotic research and development. Our objective is to build upon this unique connection and delve into the discovery of additional arsenic-containing antibiotics. This endeavor holds the potential to broaden the spectrum of resources available for combating infectious diseases and tackling the growing challenge of antibiotic resistance.
The gene set (so-called biosynthetic gene cluster, or BGC) required for arsinothricin biosynthesis were used to search sequenced genome database, which let to the discovery of several prospective BGCs for arsenic-containing antibiotics. Among them, our target is those for arsenic-containing RiPPs (Ribosomally synthesized and Post-translationally modified Peptides), especially the one from Microbispora rosea. From our target RiPP BGC, we selected four genes, which we hypothesize are the minimum required to produce an arsenic-containing precursor of the encoded RiPP, and used them to transformed Escherichia coli using a two-plasmid system. Expression of the transformed genes in E. coli was analyzed using SDS-PAGE, however, some of the gene-encoded proteins were not properly expressed. To solve the expression issue, we are currently optimizing the condition. Given that arsenic-containing peptides have never been discovered in the nature, the discovery of arsenic-containing RiPP antibiotics will not only support our hypothesis but also have a big impact over the related fields.