Understanding how antibiotic scaffolds are created in nature can help scientists prospect for brand new categories of antibiotics via DNA sequencing and genome mining. Researchers have used this information to help solve the X-ray crystal formation of the enzyme that makes obafluorin—a broad-spectrum antibiotic agent caused by a fluorescent strain of soil microorganism. The latest research from Washington University in St. Louis and the University at Buffalo is printed July 31 in the journal Nature Communications.
A multi-part enzyme known as a nonribosomal peptide synthetase creates the highly reactive beta-lactone ring that’s responsible for obafluorin’s antimicrobial exercise.
These chemical substances could be used as next-gen antibiotics for people, or even to benefit the agriculture industry, Wencewicz noted—as researchers strive to engineer seed therapies and biopesticides to help plant techniques capable of making sufficient food to feed the 9.6 billion folks projected to live on this planet by 2050.
The study provides a useful road map that reveals how individual protein domains in the ObiF1 enzyme are sutured together in three-dimensional space. An enzyme’s formation is key to nearly every task it performs.
Obafluorin is made by a fluorescent pressure of soil microorganism that forms biofilms on plant roots. Obafluorin was initially discovered in 1984, but it surely wasn’t until 2017 that Wencewicz revealed the genetic blueprint of the enzyme that creates the molecule’s bio-active elements. That discovery indicated the first time that anyone had been able to pin down a beta-lactone collecting enzyme from nature, and recreate it in the laboratory.
Researchers in the Wencewicz laboratory was able to speed up the discovery process using genetics to zero in on the biosynthetic equipment that microorganism use to make obafluorin, after which to rebuild that multi-step, enzyme-catalyzed procedure in the lab.