Friulimicins: Novel Lipopeptide Antibiotics with Peptidoglycan Synthesis Inhibiting Activity from Actinoplanes friuliensis sp. nov. I. Taxonomic Studies of the Producing Microorganism and Fermentation.

Aretz, Werner; Meiwes, Johannes; Seibert, Gerhard; Vobis, Gernot; Wink, Joachim

doi:10.7164/antibiotics.53.807

Cited by 63 publications

(46 citation statements)

References 32 publications

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“…At the time of writing, the genus Actinoplanes comprises 39 species with validly published names (Parte, 2014). Some antibiotics have been shown to be produced by strains of species of Actinoplanes such as lipiarmycin (anti Gram-positive bacteria activity), teicoplanin (inhibits cell wall synthesis of Gram-positive bacteria) and friulimicin (has peptidoglycan synthesis inhibiting activity) from Actinoplanes deccanensis, Actinoplanes teichomyceticus and Actinoplanes friuliensis, respectively (Aretz et al, 2000;Coronelli et al, 1975;Somma et al, 1984).We have attempted to find a novel source, other than terrestrial soils, for isolating novel actinomycetes. Recent studies have described the isolation of different species of actinomycete from lichen, such as Actinomycetospora iriomotensis (Yamamura et al, 2011a), Actinomycetospora rishiriensis (Yamamura et al, 2011b) and Nocardioides exalbidus (Li et al, 2007).…”

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Actinoplanes lichenis sp. nov., isolated from lichen

Phongsopitanun

Matsumoto

Inahashi

et al. 2016

International Journal of Systematic and Evolutionary Microbiology

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A novel species of the genus Actinoplanes, strain LDG1-22 T , for which we propose the name Actinoplanes lichenis sp. nov., was isolated from a lichen sample collected from tree bark in Thailand. The taxonomic position of the species has been described based on a polyphasic approach. Strain LDG1-22 T produced irregular sporangia on agar media. It contained mesodiaminopimelic acid in the cell-wall peptidoglycan. The major menaquinone was MK-9(H 4 ); the polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannosides and phosphatidylglycerol. Whole-cell hydrolysates contained ribose, glucose, mannose and small amounts of arabinose and xylose. The major cellular fatty acids were anteiso-C 15 : 0 (31.2 %) and iso-C 16 : 0 (14.2 %). Mycolic acids were absent. The G+C content was 73.6 %. 16S rRNA gene sequence analysis of strain LDG1-22 T showed highest similarity (98.8 %) to Actinoplanes friuliensis DSM 45797 T and it clustered with Actinoplanes nipponensis JCM 3264 T and Actinoplanes missouriensis JCM 3121 T in phylogenetic tree analysis. On the basis of the phenotypic characteristics and DNA-DNA relatedness, strain LDG1-22 T could be distinguished from related species of the genus Actinoplanes and so represents a novel species of this genus. The type strain of Actinoplanes lichenis sp. nov. is LDG1-22 T (5JCM 30485 T 5TISTR 2343 T 5PCU 344 T ).The genus Actinoplanes, which belongs to the family Micromonosporaceae, was first described by Couch (1950). Members of this genus can be differentiated from other related genera in the family Micromonosporaceae by considering phenotypic characteristics, especially the formation of sporangia as well as the presence of motile spores and from chemotaxonomic characteristics, including 16S rRNA gene sequence-based phylogenetic clustering (Vobis et al., 2012). As with most actinomycetes, strains of species of the genus Actinoplanes are widely distributed in soils from various environments around the world (Couch, 1963;Parenti & Coronelli, 1979;Vobis et al., 2012). At the time of writing, the genus Actinoplanes comprises 39 species with validly published names (Parte, 2014). Some antibiotics have been shown to be produced by strains of species of Actinoplanes such as lipiarmycin (anti Gram-positive bacteria activity), teicoplanin (inhibits cell wall synthesis of Gram-positive bacteria) and friulimicin (has peptidoglycan synthesis inhibiting activity) from Actinoplanes deccanensis, Actinoplanes teichomyceticus and Actinoplanes friuliensis, respectively (Aretz et al., 2000;Coronelli et al., 1975;Somma et al., 1984).We have attempted to find a novel source, other than terrestrial soils, for isolating novel actinomycetes. Recent studies have described the isolation of different species of actinomycete from lichen, such as Actinomycetospora iriomotensis (Yamamura et al., 2011a), Actinomycetospora rishiriensis (Yamamura et al., 2011b) and Nocardioides exalbidus (Li et al., 2007). In the course of our investigation into the diversi...

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confidence: 99%

Actinoplanes lichenis sp. nov., isolated from lichen

Phongsopitanun

Matsumoto

Inahashi

et al. 2016

International Journal of Systematic and Evolutionary Microbiology

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“…This compound is highly active against multidrug-resistant gram-positive bacteria, such as methicillinresistant Staphylococcus aureus strains (4). The biosynthesis of this lipopeptide is catalyzed by nonribosomal peptide synthetases (NRPS) (15).…”

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Sequencing and Analysis of the Biosynthetic Gene Cluster of the Lipopeptide Antibiotic Friulimicin in Actinoplanes friuliensis

Müller

Nolden

Gebhardt

et al. 2007

Antimicrob Agents Chemother

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Actinoplanes friuliensis produces the lipopeptide antibiotic friulimicin, which is a cyclic peptide with one exocyclic amino acid linked to a branched-chain fatty acid acyl residue. The structural relationship to daptomycin and the excellent antibacterial performance of friulimicin make the antibiotic an attractive drug candidate. The complete friulimicin biosynthetic gene cluster of 24 open reading frames from A. friuliensis was sequenced and analyzed. In addition to genes for regulation, self-resistance, and transport, the cluster contains genes encoding peptide synthetases, proteins involved in the synthesis and linkage of the fatty acid component of the antibiotic, and proteins involved in the synthesis of the nonproteinogenic amino acids pipecolinic acid, methylaspartic acid, and 2,3-diaminobutyric acid. By using heterologous gene expression in Escherichia coli, we provide biochemical evidence for the stereoselective synthesis of L-pipecolinic acid by the deduced protein of the lysine cyclodeaminase gene pip. Furthermore, we show the involvement of the dabA and dabB genes in the biosynthesis of 2,3-diaminobutyric acid by gene inactivation and subsequent feeding experiments.In recent years, the sequences of numerous gene clusters involved in the synthesis of many secondary metabolites have become available for comparison and exploitation. The programmed manipulation of genes encoding enzymes in the biosynthetic pathways offers promise for redesigning existing antibiotic structures to create antibiotics with new activities and the ability to overcome bacterial resistance (50). Therefore, each newly analyzed gene cluster represents a new tool for combinatorial biosynthesis and can provide information about the synthesis of unusual building blocks, such as nonproteinogenic amino acids, acyl residues, and sugar moieties. An interesting group of secondary metabolites for such experiments seems to be bioactive lipopeptides isolated from streptomycetes. So far, only a few biosynthetic gene clusters corresponding to these lipopeptides have been isolated and characterized, such as the clusters for calcium-dependent antibiotic (CDA) from Streptomyces coelicolor (17), daptomycin from Streptomyces roseosporus (26), and A54145 from Streptomyces fradiae (24). By targeted modification and gene exchange, it is possible to generate new lipopeptide structures (12,25).Another member of this group of secondary metabolites is the antibiotic friulimicin that is produced by the actinomycete Actinoplanes friuliensis. This compound is highly active against multidrug-resistant gram-positive bacteria, such as methicillinresistant Staphylococcus aureus strains (4). The biosynthesis of this lipopeptide is catalyzed by nonribosomal peptide synthetases (NRPS) (15).The eight bioactive lipopeptides isolated from A. friuliensis (4) consist of 10 amino acids that form a ring structure with one exocyclic amino acid linked to an acyl residue of various chain lengths. The acyl residue is a branched-chain fatty acid with a ⌬cis3 double bond. The ...

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“…For purification of friulimicin and the friulimicin derivative FR242 from culture supernatants, the wild-type and mutant MEHB were each cultivated in 100 ml seed medium (Aretz et al, 2000) in a 500 ml Erlenmeyer flask for 5 days at 30 uC on a rotary shaker at 180 r.p.m. Antibiotic production medium (Aretz et al, 2000; 26 500 ml in 1 l Erlenmeyer flasks) was inoculated with 5 ml of culture grown on seed medium and cultivated for 7 days at 30 uC at 180 r.p.m. Cells were removed by centrifugation at 5000 g and the supernatant was loaded onto a column packed with 100 ml degassed XAD-16 resin (Rohm and Haas) and equilibrated with 10 mM potassium phosphate buffer (pH 7?2).…”

Section: Methodsmentioning

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“…Eight lipopeptides recently identified and isolated from the actinomycete Actinoplanes friuliensis (Aretz et al, 2000) are composed of an identical cyclic peptide structure of ten amino acids. The peptide core is N-terminally linked via diaminobutyric acid to an acylated, exocyclic amino acid, either asparagine or aspartate (Fig.…”

Section: Introductionmentioning

confidence: 99%

An acyl-CoA dehydrogenase is involved in the formation of the Δcis3 double bond in the acyl residue of the lipopeptide antibiotic friulimicin in Actinoplanes friuliensis

et al. 2005

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The lipopeptide antibiotic friulimicin, produced by Actinoplanes friuliensis, is an effective drug against Gram-positive bacteria, such as methicillin-resistant Staphylococcus epidermidis and Staphylococcus aureus strains. Friulimicin consists of a cyclic peptide core of ten amino acids and an acyl residue linked to an exocyclic amino acid. The acyl residue is essential for antibiotic activity, varies in length from C13 to C15, and carries a characteristic double bond at position Dcis3. Sequencing of a DNA fragment adjacent to a previously described fragment encoding some of the friulimicin biosynthetic genes revealed several genes whose gene products resemble enzymes of lipid metabolism. One of these genes, lipB, encodes an acyl-CoA dehydrogenase homologue. To elucidate the function of the LipB protein, a lipB insertion mutant was generated and the friulimicin derivative (FR242) produced by the mutant was purified. FR242 had antibiotic activity lower than friulimicin in a bioassay. Gas chromatography showed that the acyl residue of wild-type friulimicin contains a double bond, whereas a saturated bond was present in FR242. These results were confirmed by the heterologous expression of lipB in Streptomyces lividans T7, which led to the production of unsaturated fatty acids not found in the S. lividans T7 parent strain. These results indicate that the acyl-CoA dehydrogenase LipB is involved in the introduction of the unusual Dcis3 double bond into the acyl residue of friulimicin.

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Friulimicins: Novel Lipopeptide Antibiotics with Peptidoglycan Synthesis Inhibiting Activity from Actinoplanes friuliensis sp. nov. I. Taxonomic Studies of the Producing Microorganism and Fermentation.

Cited by 63 publications

References 32 publications

Actinoplanes lichenis sp. nov., isolated from lichen

Actinoplanes lichenis sp. nov., isolated from lichen

Sequencing and Analysis of the Biosynthetic Gene Cluster of the Lipopeptide Antibiotic Friulimicin in Actinoplanes friuliensis

An acyl-CoA dehydrogenase is involved in the formation of the Δcis3 double bond in the acyl residue of the lipopeptide antibiotic friulimicin in Actinoplanes friuliensis

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