Plantazolicin (PZN) is a natural antibiotic produced by the

gram-positive In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. Gram-positive bact ...

soil bacterium ''Bacillus velezensis'' FZB42 (previously ''

Bacillus amyloliquefaciens ''Bacillus amyloliquefaciens'' is a species of bacterium in the genus ''Bacillus'' that is the source of the BamHI restriction enzyme. It also synthesizes a natural antibiotic protein barnase, a widely studied ribonuclease that forms a famously t ...

'' FZB42). PZN has specifically been identified as a selective bactericidal agent active against '' Bacillus anthracis'', the causative agent of anthrax. This natural product is a ribosomally synthesized and post-translationally modified

peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. ...

(RiPP); it can be classified further as a thiazole/oxazole-modified microcin (TOMM) or a linear

azole Azoles are a class of five-membered heterocyclic compounds containing a nitrogen atom and at least one other non-carbon atom (i.e. nitrogen, sulfur, or oxygen) as part of the ring. Their names originate from the Hantzsch–Widman nomenclature. T ...

-containing

(LAP). 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''.

History

The genes for the biosynthesis of PZN were first reported in 2008. The natural product was then isolated in 2011 from ''

''. The structure of PZN was solved later that year by two independent research groups, primarily through high-resolution mass spectrometry and

NMR spectroscopy Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy or magnetic resonance spectroscopy (MRS), is a spectroscopic technique to observe local magnetic fields around atomic nuclei. The sample is placed in a magnetic fie ...

. In 2013, various biomimetic chemical synthesis studies of PZN were reported, including a

total synthesis Total synthesis is the complete chemical synthesis of a complex molecule, often a natural product, from simple, commercially-available precursors. It usually refers to a process not involving the aid of biological processes, which distinguishes i ...

Biosynthesis

In bacteria, plantazolicin (PZN) is synthesized first as an unmodified peptide via

translation Translation is the communication of the meaning of a source-language text by means of an equivalent target-language text. The English language draws a terminological distinction (which does not exist in every language) between ''transla ...

at the ribosome. A series of enzymes then chemically alter the peptide to install its post-translational modifications, including several

heterocycle A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring(s). Heterocyclic chemistry is the branch of organic chemistry dealing with the synthesis, properties, and ...

s and an N-terminal

amine In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen Hydrogen is the chemical element wi ...

dimethylation. 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 (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 A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the for ...

contained in the biosynthetic

gene cluster A gene family is a set of homologous genes within one organism. A gene cluster is a group of two or more genes found within an organism's DNA that encode similar polypeptides, or proteins, which collectively share a generalized function and are ...

. Following leader peptide removal, the newly formed N-terminus undergoes methylation to yield an . This final modification results in mature PZN. Other organisms such as ''

Bacillus pumilus ''Bacillus pumilus'' is a Gram-positive, aerobic, spore-forming bacillus commonly found in soil. ''Bacillus pumilus'' spores—with the exception of mutant strain ATCC 7061—generally show high resistance to environmental stresses, including ...

'', '' Clavibacter michiganensis subsp. sepedonicus'', '' Corynebacterium urealyticum '', and'' Brevibacterium linens '' have been identified with similar gene clusters that have the potential to produce PZN-like molecules.

References

{{reflist Bactericides Antibiotics Peptides Oxazolines Oxazoles Thiazoles