The significance of PZN stems from its narrow-spectrum antibiotic activity. Most antibiotics in clinical use are
broad-spectrum, acting against a wide variety of bacteria, and
antibiotic resistance to these drugs is common. In contrast, PZN is antibacterial against only a small number of species, including Bacillus anthracis.[citation needed]
The biosynthesis of plantazolicin (PZN) entails modification of a precursor peptide by several enzymes.
In bacteria, plantazolicin (PZN) is synthesized first as an unmodified peptide via
translation at the
ribosome. A series of
enzymes then chemically alter the peptide to install its post-translational modifications, including several
azoleheterocycles and an N-terminal
amine dimethylation.[citation needed]
Specifically, during the biosynthesis of PZN in B. velezensis, a ribosomally-synthesized precursor peptide undergoes extensive post-translational modification, including cyclodehydrations and dehydrogenations, catalyzed by a trimeric enzyme complex. This process converts
cysteine and
serine/
threonine residues into thiazole and (methyl)oxazole heterocycles[7] (as seen to the right).
The exact mechanism of the association of the trimeric enzyme complex with the N-terminal leader peptide region is not yet understood; however, it is thought that the leader peptide is cleaved from the core peptide putatively by the
peptidase contained in the biosynthetic
gene cluster.[9] Following leader peptide removal, the newly formed N-terminus undergoes methylation to yield an Nα,Nα-dimethylarginine. This final modification results in mature PZN.[citation needed]
^Banala, Srinivas; Ensle, Paul; Süssmuth, Roderich D. (2013). "Total Synthesis of the Ribosomally Synthesized Linear Azole-Containing Peptide Plantazolicin a from Bacillus amyloliquefaciens". Angewandte Chemie International Edition. 52 (36): 9518–9523.
doi:
10.1002/anie.201302266.
PMID23761292.