Antibiotic production by bacteria
involves complex chemistry that is often encoded in a collection or
'cluster' of many genes. To express these giant gene clusters requires
special regulation mechanisms. Understanding these mechanisms could help
a great deal in the search for new antibiotics produced by bacteria.
A new protein that likely will advance the
search for new natural antibiotics has been discovered by scientists. The study by Texas
A&M AgriLife Research is published in the journal Nature Microbiology
‘The newly discovered protein, named long operon associated protein (LoaP), is frequently found next to the gene clusters that are responsible for producing antibiotics. Hence, knowing how LoaP works and its prime location could lead scientists to a shortcut for antibiotic production.’
The discovery has to do with how proteins regulate gene
expression. Scientists know a great deal about proteins that control how
certain gene clusters get their start - referred to as transcription
initiation - but much less is known about transcription elongation
where proteins keep gene expression going through "roadblocks" in the
DNA sequence, according to Dr. Paul Straight, AgriLife Research
biochemist in College Station and the paper's co-author.
"The upshot is that our discovery expands the basic knowledge of
processive antitermination - a type of genetic regulation - and
demonstrates that the mechanism is more widespread among bacteria than
previously thought," Straight said.
For this study, Straight and his graduate assistant Chengxi Zhang
of College Station, teamed up with University of Maryland researchers
Jonathan R. Goodson, Steven Klupt and Dr. Wade Winkler.
The team describes two discoveries in the paper. One is the
protein they named LoaP, which stands for long operon associated
protein. The other discovery is that the protein is frequently found
next to the gene clusters that are responsible for producing
antibiotics. Hence, knowing how LoaP works and its prime location could
lead scientists to a shortcut for antibiotic production.
Straight explained that bacteria frequently string together many
genes, which are expressed as a group when the cell needs the proteins
the genes encode.
"These long chains of genes raise challenges for the molecular
machines that decode DNA. Sometimes the molecular machines hit
roadblocks, called terminators, and they stop and fall off the DNA. The
LoaP protein is called a processive antiterminator, because it helps the
machines stay on DNA and move through the roadblock terminators."
The team discovered the LoaP protein in Bacillus amyloliquefaciens
, a bacteria known to ward off pathogens that attack plant roots in agriculture, aquaculture and hydroponic production.
The researchers said the Earth has an abundant and diverse supply
of microbes such as bacteria and many of them have useful biomedical
purposes. While researchers realize the potential benefits - and indeed
have been studying them for more than 100 years - a modern limitation
to antibiotic discovery is the murky understanding of the genetic
regulatory mechanisms that oversee their production.
"After nearly a century of searching for bioactive natural
products, bacteria still constitute a major target of modern drug
discovery," Straight said. "The characterization of the biochemical
pathways of these molecules remains a bottleneck to their development.
One of the key restrictions is a shortage of knowledge on the range of
genetic mechanisms that can affect them. Therefore, the discovery of new
classes of genetic regulatory mechanisms is likely to impact future
development of natural products that counter disease."