Difficidin and oxydifficidin: Novel broad spectrum antibacterial antibiotics produced by Bacillus subtilis. II. Isolation and physico-chemical characterization.

Wilson, Kenneth E.; Flor, James E.; Schwartz, Robert E.; Joshua, H; Smith, Jack L.; Pelak, Barbara A.; Liesch, Jerrold M.; Hensens, Otto D.

doi:10.7164/antibiotics.40.1682

Cited by 49 publications

(42 citation statements)

References 2 publications

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“…In particular, peaks were observed at m/z 583.3, 605.3, 621.3, and 637.3 which were attributed to mono-and dialkali ion adducts of these compounds (data not shown). Wilson et al (51) showed that difficidin is phosphorylated. In agreement, alkali adducts of the dephosphorylated species were detected at m/z 487.4 and 503.3 (difficidin), as well as at m/z 503.4 and 519.4 (oxydifficidin).…”

Section: Discoverymentioning

confidence: 99%

“…The corresponding compounds were identified by comparison with MS data available for the polyketides of B. subtilis ATCC 39320 and B. subtilis 1A/3 (15,51) and attributed to the polyene antibiotics bacillaene and difficidin (33,51 Difficidin and its oxidized form oxydifficidin appeared mainly as their alkali ion adducts, whereas the intensity of the mass peaks of their protonated forms at m/z 545.3 and 561.3 are very low. Oxydifficidin bears a hydroxyl group at position 5 of the difficidin ring system (51) showing mass signals 16 mass units higher than those of the main metabolite. In particular, peaks were observed at m/z 583.3, 605.3, 621.3, and 637.3 which were attributed to mono-and dialkali ion adducts of these compounds (data not shown).…”

Section: Discoverymentioning

confidence: 99%

“…Production of polyketide-like compounds with antibacterial activity by wild-type isolates of B. subtilis has been described previously (15). The polyene antibiotics difficidin and oxydifficidin are highly unsaturated 22-member macrolides with a rare phosphate group (51). Another antibiotic, bacillaene, was demonstrated to be a conjugated hexaene with a linear structure (33), but its chemical structure is still un-known.…”

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Structural and Functional Characterization of Three Polyketide Synthase Gene Clusters in Bacillus amyloliquefaciens FZB 42

et al. 2006

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Although bacterial polyketides are of considerable biomedical interest, the molecular biology of polyketide biosynthesis in Bacillus spp., one of the richest bacterial sources of bioactive natural products, remains largely unexplored. Here we assign for the first time complete polyketide synthase (PKS) gene clusters to Bacillus antibiotics. Three giant modular PKS systems of the trans-acyltransferase type were identified in Bacillus amyloliquefaciens FZB 42. One of them, pks1, is an ortholog of the pksX operon with a previously unknown function in the sequenced model strain Bacillus subtilis 168, while the pks2 and pks3 clusters are novel gene clusters. Cassette mutagenesis combined with advanced mass spectrometric techniques such as matrixassisted laser desorption ionization-time of flight mass spectrometry and liquid chromatography-electrospray ionization mass spectrometry revealed that the pks1 (bae) and pks3 (dif) gene clusters encode the biosynthesis of the polyene antibiotics bacillaene and difficidin or oxydifficidin, respectively. In addition, B. subtilis OKB105 (pheA sfp 0 ), a transformant of the B. subtilis 168 derivative JH642, was shown to produce bacillaene, demonstrating that the pksX gene cluster directs the synthesis of that polyketide.Environmental Bacillus amyloliquefaciens strain FZB 42 is distinguished from the domesticated model organism Bacillus subtilis 168 (23) by several features important for rhizosphere competence particularly by its abilities to suppress competitive organisms present in the plant rhizosphere (17, 21) and to promote plant growth (16). In a previous contribution (20), we have reported that B. amyloliquefaciens FZB 42 is a producer of three families of lipopeptides, surfactins, bacillomycins D, and fengycins, which are well-known secondary metabolites with mainly antifungal activity. They are also produced by numerous B. subtilis strains (48). Furthermore, three giant gene clusters containing genes with homology to polyketide synthase (PKS) genes of modular organization were identified but not assigned functional roles. Mutants of FZB 42 deficient in the synthesis of cyclic lipopeptides were unable to suppress phytopathogenic fungi but still retained their antibacterial potency.Polyketides belong to a large family of secondary metabolites that include many bioactive compounds with antibacterial, immunosuppressive, antitumor, or other physiologically relevant bioactivities. Their biosynthesis is accomplished by stepwise decarboxylative Claisen condensations between the extender unit and the growing polyketide chain, generating enzyme-bound ␤-ketoacyl intermediates. Before a subsequent round of chain extension, a variable set of modifying enzymes can locally introduce structural variety. Similar to the nonribosomal synthesis of peptides, the PKS multienzyme system uses acyl carrier proteins (ACPs) that are posttranslationally modified with the 4Ј-phosphopantetheine prosthetic group to channel the growing polyketide intermediate during elongation processes (3). Type I PKSs...

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Section: Discoverymentioning

confidence: 99%

Section: Discoverymentioning

confidence: 99%

mentioning

confidence: 99%

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Structural and Functional Characterization of Three Polyketide Synthase Gene Clusters in Bacillus amyloliquefaciens FZB 42

et al. 2006

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“…For instance, three functional gene clusters directing the synthesis of difficidin, macrolactin and bacillaene were identified in B. amyloliquefaciens (Arguelles-Arias et al, 2009;Chen et al, 2007). Difficidin is an unsaturated 22-membered macrocylic polyene lactone phosphate ester with broadspectrum antibacterial activity (Wilson et al, 1987;Zimmerman et al, 1987). It inhibits protein biosynthesis and was recently shown promising in its suppressive action against Erwinia amylovara, a devasting plant pathogen causing necrotrophic fire blight disease of apple, pear and other rosaceous plants (Zweerink and Edison, 1987;Chen et al, 2009b).…”

Section: Introductionmentioning

confidence: 99%

Antibiotic Compounds from <i>Bacillus</i>: Why are they so Amazing?

Fickers

2012

American Journal of Biochemistry and Biotechnology

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Abstract:The constant increase of multi-drug resistant pathogens stimulates research, more than ever, to identify and develop new antibacterial compounds. The recent advances in genome sequencing have highlighted the genus Bacillus as an unexpected source of antibiotic-like compounds. This review focus on the different class of antimicrobial molecules produce by Bacillus genus such as polyketides, nonribosomal peptide, bacteriocins as well as other unusual peptides.

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“…The biosynthesis of difficidin is performed by the dfn gene cluster and with the structure of a highly unsaturated macrocyclic polyene lactone phosphate ester (Wilson et al, 1987). Difficidin has demonstrated a broad spectrum of antimicrobial activity against both aerobic and anaerobic bacteria.…”

Section: Polyketidesmentioning

confidence: 99%

Microbial Community Structure and Functionality in Ruminants Fed the Probiotic Bacillus amyloliquefaciens H57

Schofield¹

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In the agricultural industry, farmers are continually searching for ways to improve animal production. Developing a more efficient digestive system is one such way that this can be achieved.In domesticated ruminants such as sheep and cattle, the feed material is initially digested in the largest and most prominent compartment of the alimentary canal: the rumen. The rumen is populated by a complex community of microorganisms that are capable of degrading the tough fibrous components of the plant cell wall, releasing fermentable and digestible carbohydrates, proteins, lipids and nucleic acids. Probiotics, defined as "live microorganisms that, when administered in adequate amounts, confer a health benefit on the host", have been used as a means to influence the rumen microbial community to improve the efficiency of feed digestion.In this study we cultivate the probiotic Bacillus amyloliquefaciens strain H57 as an inoculum, to be added to pelleted animal feed in concentrations of 10 9 cfu kg -1 (Chapter 2). To determine the genetic makeup of H57, its genome was sequenced (Chapter 3). The sequence analysis revealed a number of antimicrobial lipopeptides and polyketides, which if expressed in the rumen could significantly alter the rumen microbial community. Other genes of interest within the H57 genome include a number of carbohydrate degrading enzymes as well as those involved with nitrate reduction, which has been recognised as a potential alternative electron acceptor under anaerobic conditions such as the rumen.The H57 inoculum was administered in two animal feeding trials, one using pregnant Dorper ewes and the other using newborn dairy calves. In both instances a significant increase in weight gain was observed in the H57 fed animals compared to the control group. As a means to understand how H57 benefits these animals, the rumen microbial community was profiled by sequencing PCR amplicons of the 16S rRNA gene (Chapter 4). Analysis of the calf rumen microbiome did not reveal any significant differences between the control calves and those that were fed H57 for eight weeks. The only differences in the rumen community occurred between the initial sampling at four weeks and after weaning at eight weeks. In the sheep, however, there was a clear shift in microbial community structure between the control and H57 fed sheep. In both the control and H57 fed sheep the most abundant bacterial populations were Prevotella, although different species were dominant in each treatment group. The H57 fed sheep also had an abundance of Roseburia.Further analysis into the genetic potential and functionality of differentially abundant rumen microorganisms was performed on the sheep samples using metagenomic and metatranscriptomic sequencing. It was found that in the H57 fed sheep the rumen microbial community had an increased expression of hemicellulolytic enzymes, including β-glucosidase/β-galactosidase, α-galactosidase and L-arabinose isomerase. As hemicellulose contributes a significant portion of plant iii cell wall bio...

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Difficidin and oxydifficidin: Novel broad spectrum antibacterial antibiotics produced by Bacillus subtilis. II. Isolation and physico-chemical characterization.

Cited by 49 publications

References 2 publications

Structural and Functional Characterization of Three Polyketide Synthase Gene Clusters in Bacillus amyloliquefaciens FZB 42

Structural and Functional Characterization of Three Polyketide Synthase Gene Clusters in Bacillus amyloliquefaciens FZB 42

Antibiotic Compounds from <i>Bacillus</i>: Why are they so Amazing?

Microbial Community Structure and Functionality in Ruminants Fed the Probiotic Bacillus amyloliquefaciens H57

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