Structural characterization of a lipopeptide antibiotic A54145E(Asn3Asp9) produced by a genetically engineered strain of Streptomyces fradiae

Gu, Jian-Qiao; Alexander, Dylan C.; Rock, Jessica L.; Brian, Paul; Chu, Min; Baltz, Richard H.

doi:10.1038/ja.2010.140

Cited by 12 publications

(14 citation statements)

References 24 publications

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“…The sample was purified by LH-20 gel chromatography, using 60% methanol as the mobile phase and 1 mL/min flow rate (Nguyen et al, 2010; Gu et al, 2011; Li et al, 2012). The sample was collected at the peak of retention time 55.166 min, and then purified using rotary evaporation for the following antibacterial activity test.…”

Section: Methodsmentioning

confidence: 99%

Characterization of Lipopeptide Biosurfactants Produced by Bacillus licheniformis MB01 from Marine Sediments

et al. 2017

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Antibiotic resistance has become one of the world’s most severe problems because of the overuse of antibiotics. Antibiotic-resistant bacteria are more difficult to kill and more expensive to treat. Researchers have been studied on antibiotic alternatives such as antimicrobial peptides and lipopeptides. A functional bacteria MB01 producing lipopeptides which can be used as bacteriostat was isolated from the Bohai Sea sediments, which had been identified as Bacillus licheniformis by the morphological, physiological, and biochemical identification and 16s rDNA sequence. The lipopeptides produced by MB01 were determined to be cyclic surfactin homologs by LC-ESI-MS structural identification after crude extraction and LH-20 chromatography. [M+H]+ m/z 994, 1008, 1022, and 1036 were all the characteristic molecular weight of surfactin homologs. CID analysis revealed that the molecular structure of the lipopeptides was Rn-Glu1-Leu/Ile2-Leu3-Val4-Asp5-Leu6-Leu/Ile7. The lipopeptides showed well resistance to UV light and the change of pH and temperature.

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Section: Methodsmentioning

confidence: 99%

Characterization of Lipopeptide Biosurfactants Produced by Bacillus licheniformis MB01 from Marine Sediments

et al. 2017

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“…CB-182,390 (Asn 3 , Asp 9 and 3mGlu 12 ) was targeted for further investigation, including extensive chemical analyses, including amino acid quantitation, tandem LC-MS-MS analysis and 2D-NMR to confirm the structure. 24 Potent antibacterial activity depends on the presence of modified amino acids, making total peptide synthesis or chemoenzymatic synthesis, 30 utilizing proteinogenic amino acids undesirable approaches to generate A54145 analogs. As chemical synthesis of the chiral modified amino acids at the necessary scale for SAR studies is not practical, combinatorial biosynthesis 19 remains the most effective method to generate potent novel lipopeptides.…”

Section: Discussionmentioning

confidence: 99%

“…18 Engineered strains producing novel lipopeptides were scaled up to 5 l of DSF-Ile in multiple shake flasks and centrifuged culture supernatant was purified by column chromatography using HP20 resin and semipreparative HPLC as described. 24 Only the major lipopeptide produced in DSF-Ile media, containing Ile 13 and anteiso-undecanoyl side chain was purified and characterized. LC-MS-MS analysis of select lipopeptides was carried out as described.…”

Section: Fermentation Measurement Of Lipopeptide Production and Purimentioning

confidence: 99%

Production of novel lipopeptide antibiotics related to A54145 by Streptomyces fradiae mutants blocked in biosynthesis of modified amino acids and assignment of lptJ, lptK and lptL gene functions

Alexander

Rock

et al. 2010

J Antibiot

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A54145 is a complex of lipopeptide antibiotics produced by Streptomyces fradiae. A54145 factors are structurally related to daptomycin, with four modified amino acids, only one of which is present in daptomycin. We generated three mutants defective in lptJ, lptK or lptL, whose gene products are involved in the formation of hydroxy-Asn 3 (hAsn 3 ) and methoxy-Asp 9 (moAsp 9 ). Each of the mutants produced novel lipopeptides related to A54145 and the profiles allowed assignment of functions for those genes. We constructed strains carrying different combinations of these genes coupled with a mutation in the lptI gene involved in the biosynthesis of 3-methyl-Glu 12 (3mGlu 12 ), and all recombinants produced novel lipopeptides. One of the compounds displayed very good antibacterial activity in the presence of bovine surfactant, which interacts with daptomycin or A54145E to inhibit their antibacterial activities. (Figure 1) is a complex of calcium-dependent lipodepsipeptide antibiotics produced by Streptomyces fradiae NRRL 18160. 1,2 A54145 has a cyclic depsipeptide ring containing 10 amino acids and an exocyclic tail of three amino acids, and it is similar in overall structure to daptomycin. Like A21987C and daptomycin, 3,4 the Nterminal Trp 1 of the exocyclic peptide is coupled to long-chain length fatty acids, the most common being iso-decanoyl, n-decanoyl and anteiso-undecanoyl in A54145 factors. 1,2 A54145 factors also vary at positions 12 and 13, in which different factors have different combinations of Glu 12 , L-3-methyl-Glu 12 (3mGlu 12 ), Ile 13 , or Val 13 . The most prevalent factors produced during the S. fradiae fermentation are shown in Figure 1. Typically, A54145 factors containing Glu 12 accumulate early in fermentation and those containing 3mGlu 12 accumulate later, with final yields of about 60% of factors containing Glu 12 . 1 The study by Boeck et al. 5 demonstrated that the distribution of A54145 factors can be manipulated by adding certain amino acids or lipids to the fermentation. For instance, feeding L-Ile, enriched for factors containing Ile 13 from 89 to 98%, whereas feeding L-Val (which inhibited overall lipopeptide production by about 70%) enriched for compounds containing Val 13 from 11 to 56%, almost exclusively in

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“…Cell-surface studies suggest that D-peptides have the potential to be used for intravenous injection and direct-surface application as antiinfectives (Monk et al 2005). A potent new lipopeptide antibiotic isolated from Streptomyces fradiae contains three D-amino acids (Gu et al 2010). A designed D-peptide shows promise as a potent antiviral candidate against HIV (Welch et al 2010).…”

Section: D-peptidesmentioning

confidence: 99%

Nutritional and medicinal aspects of d-amino acids

2011

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This paper reviews and interprets a method for determining the nutritional value of D-amino acids, D-peptides, and amino acid derivatives using a growth assay in mice fed a synthetic all-amino acid diet. A large number of experiments were carried out in which a molar equivalent of the test compound replaced a nutritionally essential amino acid such as L-lysine (L-Lys), L-methionine (L-Met), L-phenylalanine (L-Phe), and L-tryptophan (L-Trp) as well as the semi-essential amino acids L-cysteine (L-Cys) and L-tyrosine (L-Tyr). The results show wide-ranging variations in the biological utilization of test substances. The method is generally applicable to the determination of the biological utilization and safety of any amino acid derivative as a potential nutritional source of the corresponding L-amino acid. Because the organism is forced to use the D-amino acid or amino acid derivative as the sole source of the essential or semi-essential amino acid being replaced, and because a free amino acid diet allows better control of composition, the use of all-amino-acid diets for such determinations may be preferable to protein-based diets. Also covered are brief summaries of the widely scattered literature on dietary and pharmacological aspects of 27 individual D-amino acids, D-peptides, and isomeric amino acid derivatives and suggested research needs in each of these areas. The described results provide a valuable record and resource for further progress on the multifaceted aspects of D-amino acids in food and biological samples.

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Structural characterization of a lipopeptide antibiotic A54145E(Asn3Asp9) produced by a genetically engineered strain of Streptomyces fradiae

Cited by 12 publications

References 24 publications

Characterization of Lipopeptide Biosurfactants Produced by Bacillus licheniformis MB01 from Marine Sediments

Characterization of Lipopeptide Biosurfactants Produced by Bacillus licheniformis MB01 from Marine Sediments

Production of novel lipopeptide antibiotics related to A54145 by Streptomyces fradiae mutants blocked in biosynthesis of modified amino acids and assignment of lptJ, lptK and lptL gene functions

Nutritional and medicinal aspects of d-amino acids

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