Plantazolicin A and B: Structure Elucidation of Ribosomally Synthesized Thiazole/Oxazole Peptides from <i>Bacillus amyloliquefaciens</i> FZB42

Kalyon, Bahar; Helaly, Soleiman E.; Scholz, Romy; Nachtigall, Jonny; Vater, Joachim; Borriss, Rainer; Süssmuth, Roderich D.

doi:10.1021/ol200809m

Cited by 92 publications

(79 citation statements)

References 30 publications

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“…While nonribosomal synthesis of lipopeptides and polyketides is dependent on phosphopantheine transferase, Sfp, nonribosomal synthesis of the antimicrobial dipeptide bacilysin is not dependent on Sfp [Chen et al, 2009a]. Recently, a ribosomal synthesized peptide with antibacterial activity and also contributing to the successful competing of B. amyloliquefaciens FZB42 in the rhizosphere was detected in FZB42 [Kalyon et al, 2011;Scholz et al, 2011].…”

Section: Introductionmentioning

confidence: 99%

Two-Component Response Regulator DegU Controls the Expression of Bacilysin in Plant-Growth-Promoting Bacterium Bacillus amyloliquefaciens FZB42

et al. 2012

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The plant-growth-promoting-rhizobacteria Bacillus amyloliquefaciens FZB42 possess an enormous potential to synthesize a wide range of antimicrobial, antiviral and nematocidal compounds. One of them, the dipeptide antibiotic bacilysin, is synthesized by FZB42 during exponential growth. Here, we have demonstrated that bacilysin is positively regulated by the two-component response regulator DegU at the transcriptional level. In addition, ScoC (Hpr), a transition state regulator, negatively controlled expression of the bacA gene, which is the first gene within the bacilysin operon. Both DegU and ScoC were bound directly at the bacA promoter region. Furthermore, a monocistronic gene located in close vicinity of the bac operon and essential for bacilysin production, ywfH, was also regulated by DegU. Transcription of the bac operon and of the ywfH gene in B. amyloliquefaciens FZB42 was positively controlled by the DegU global regulator protein. The role of interactions within a ternary complex formed by the antagonistically acting regulators DegU and ScoC as well as the bacA promoter sequence remains to be elucidated.

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Section: Introductionmentioning

confidence: 99%

Two-Component Response Regulator DegU Controls the Expression of Bacilysin in Plant-Growth-Promoting Bacterium Bacillus amyloliquefaciens FZB42

et al. 2012

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“…Recently, we detected a strongly modified peptide, plantazolicin, produced by a B. amyloliquefaciens FZB42 mutant strain deficient in nonribosomal synthesis (9). The compound belongs to the TOMM group of thiazole/oxazole-modified microcins (10,11), and its structure has been elucidated to contain a hitherto unusual number of thiazoles and oxazoles formed from a linear 14-mer precursor peptide (12). It acts against closely related bacilli, especially B. anthracis (13).…”

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Amylocyclicin, a Novel Circular Bacteriocin Produced by Bacillus amyloliquefaciens FZB42

et al. 2014

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Bacillus amyloliquefaciens FZB42 is a Gram-positive plant growth-promoting bacterium with an impressive capacity to synthesize nonribosomal secondary metabolites with antimicrobial activity. Here we report on a novel circular bacteriocin which is ribosomally synthesized by FZB42. The compound displayed high antibacterial activity against closely related Gram-positive bacteria. Transposon mutagenesis and subsequent site-specific mutagenesis combined with matrix-assisted laser desorption ionization-time of flight mass spectroscopy revealed that a cluster of six genes covering 4,490 bp was responsible for the production, modification, and export of and immunity to an antibacterial compound, here designated amylocyclicin, with a molecular mass of 6,381 Da. Peptide sequencing of the fragments obtained after tryptic digestion of the purified peptide revealed posttranslational cleavage of an N-terminal extension and head-to-tail circularization of the novel bacteriocin. Homology to other putative circular bacteriocins in related bacteria let us assume that this type of peptide is widespread among the Bacillus/Paenibacillus taxon.

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“…enzymology | mutagenesis | RiPP natural product P lantazolicin (PZN) is a poly-azol(in)e-containing molecule of ribosomal origin from the plant-growth promoting bacterium, Bacillus amyloliquefaciens FZB42 (1)(2)(3). PZN exhibits selective bactericidal activity toward Bacillus anthracis (3).…”

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Structural and functional insight into an unexpectedly selective N -methyltransferase involved in plantazolicin biosynthesis

Lee

Hao

Blair³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Plantazolicin (PZN), a polyheterocyclic, N α ,N α -dimethylargininecontaining antibiotic, harbors remarkably specific bactericidal activity toward strains of Bacillus anthracis, the causative agent of anthrax. Previous studies demonstrated that genetic deletion of the S-adenosyl-L-methionine-dependent methyltransferase from the PZN biosynthetic gene cluster results in the formation of desmethylPZN, which is devoid of antibiotic activity. Here we describe the in vitro reconstitution, mutational analysis, and X-ray crystallographic structure of the PZN methyltransferase. Unlike all other known small molecule methyltransferases, which act upon diverse substrates in vitro, the PZN methyltransferase is uncharacteristically limited in substrate scope and functions only on desmethylPZN and close derivatives. The crystal structures of two related PZN methyltransferases, solved to 1.75 Å (Bacillus amyloliquefaciens) and 2.0 Å (Bacillus pumilus), reveal a deep, narrow cavity, putatively functioning as the binding site for desmethylPZN. The narrowness of this cavity provides a framework for understanding the molecular basis of the extreme substrate selectivity. Analysis of a panel of point mutations to the methyltransferase from B. amyloliquefaciens allowed the identification of residues of structural and catalytic importance. These findings further our understanding of one set of orthologous enzymes involved in thiazole/oxazole-modified microcin biosynthesis, a rapidly growing sector of natural products research.enzymology | mutagenesis | RiPP natural product P lantazolicin (PZN) is a poly-azol(in)e-containing molecule of ribosomal origin from the plant-growth promoting bacterium, Bacillus amyloliquefaciens FZB42 (1-3). PZN exhibits selective bactericidal activity toward Bacillus anthracis (3). All of the genes required for PZN production, immunity, and export cluster within a 10-kb region of the FZB42 genome (Fig. 1A). Genome mining has identified highly similar PZN biosynthetic gene clusters in Bacillus pumilus, Clavibacter michiganensis subsp. sepedonicus, Corynebacterium urealyticum, and Brevibacterium linens (3). PZN is biosynthesized from a 41-residue, inactive precursor peptide (Fig. 1A). Distinguishing chemical features of PZN are the two contiguous poly-azol(in)e moieties, which like all thiazole/oxazole-modified microcin (TOMM) natural products, originate from Cys and Ser/Thr residues on the C-terminal region of the precursor peptide (4-6). During heterocycle formation, a cyclodehydratase first converts Cys and Ser/Thr to thiazoline and (methyl)oxazoline, respectively. This ATP-dependent transformation formally removes water from the preceding amide bond (7-10). Subsequent dehydrogenation yields the aromatic thiazole and (methyl)oxazole (11). During PZN maturation, all 10 Cys and Ser/Thr residues within the C-terminal core region are cyclized, yielding 9 azole heterocycles and 1 methyloxazoline (Fig. 1B). Further modification includes leader peptide proteolysis and methylation to yield the final metabolite. The ...

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Plantazolicin A and B: Structure Elucidation of Ribosomally Synthesized Thiazole/Oxazole Peptides from Bacillus amyloliquefaciens FZB42

Cited by 92 publications

References 30 publications

Two-Component Response Regulator DegU Controls the Expression of Bacilysin in Plant-Growth-Promoting Bacterium Bacillus amyloliquefaciens FZB42

Two-Component Response Regulator DegU Controls the Expression of Bacilysin in Plant-Growth-Promoting Bacterium Bacillus amyloliquefaciens FZB42

Amylocyclicin, a Novel Circular Bacteriocin Produced by Bacillus amyloliquefaciens FZB42

Structural and functional insight into an unexpectedly selective N -methyltransferase involved in plantazolicin biosynthesis

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