Phosphonic and phosphinic acids are bioreactive compounds that have been used as antibiotics, antifungal agents, antimalarial drugs, and herbicides. Rhizocticins are naturally occurring phosphonates produced by Bacillus subtilus that have antifungal properties and interfere with the biosynthesis of the amino acid threonine. By varying the N-terminal amino acid group in the rhizocticin compound, it is possible to alter its biological activity. In particular, oligopeptides that are created by varying this amino acid could potentially allow enhanced capability for controlling selectivity for targeting particular organisms. As a result, compounds are less toxic to the host species and hold more promise for creating therapeutics. Despite the potential for making these types of compounds, organic synthesis has never been achieved due largely in part to the fact that the biosynthetic pathway has not been well understood. University of Illinois scientists have now identified the gene cluster responsible for biosynthesis of rhizocticin in B. subtilis, making biosynthesis of rhizocticin compounds possible.
Details
Original attempts to isolate and identify this unquie cluster failed, however, the genome of a specific strain of B. subtilis was sequenced and open reading frame locations were determined and annotated. Upon comparison with a non-rhizocticin-producing strain of B. subtilis, the rhizocticin biosynthetic gene cluster was able to be identified and isolated. There are more than 10 genes in the B. subtilis rhizocticin cluster. The biosynthetic pathway was proposed using sequence homology (similarity) for each of the genes. One particular gene in the cluster was identified by the inventors as being unique to this biosynthetic pathway. The cluster responsible for rhizocticin was verified by successfully inserting it into a non-producing strain of B. subtilis.
Applications
- Pharmaceutical industry: Synthesis of biologically active compounds and analogs of rhizocticin.
- Production of novel oligopeptides with therapeutic properties
- Agricultural industry: Herbicide
Benefits
The identification of specific gene cluster for biosynthesis of rhizocticin allows:
- Specific synthesis of compounds;
- Control of biological activity of compounds; and
- Control of compound toxicity in mammals