NMR structure determination and calcium binding effects of lipopeptide antibiotic daptomycin

Ball, Lee Jon; Goult, C.M.; Donarski, James; Micklefield, Jason; Ramesh, Vasudevan

doi:10.1039/b402722a

Cited by 93 publications

(106 citation statements)

References 23 publications

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“…42 Ball et al also reported the structure of Ca 2+ -bound daptomycin using an 0.8 mM solution of daptomycin at pH 5.3. 36 There were no major differences between their Ca 2+ -daptomycin structure and their apo-daptomycin structure.…”

Section: Solution Structure Of Calcium-bound Daptomycinmentioning

confidence: 89%

“…Line broadening increased up to 1 equivalent of Ca 2+ and then ceased. 36 The change in line width had a sigmoidal dependence on the amount of Ca 2+ added, suggesting cooperative binding. The addition of Ca 2+ did not result in discernible changes to chemical shifts.…”

Section: Calcium-induced Aggregation and Its Role In Daptomycin Delivmentioning

confidence: 92%

“…This question has been studied with 1 H-NMR 36,39 and optical methods. 40 In the absence of calcium and at pH 7.4 or higher, daptomycin aggregation is minimal or absent at millimolar concentrations, whereas under acidic conditions aggregates may form at concentrations as low as 0.12-0.2 mM.…”

Section: Aggregation Of Free Daptomycin In Solutionmentioning

confidence: 99%

“…36 Some aggregation of apo-daptomycin would be expected to occur under these conditions. A preferred aqueous conformation for apo-daptomycin was also reported.…”

Section: Solution Structure Of Apo-daptomycinmentioning

confidence: 99%

“…36,42 The Hancock group reported the a structure obtained using samples of 2 mM daptomycin with 5 mM Ca 2+ at pH 6.6. 42 Under these conditions, some line broadening was noted, indicating some extent of aggregation.…”

Section: Solution Structure Of Calcium-bound Daptomycinmentioning

confidence: 99%

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The action mechanism of daptomycin

Taylor

Palmer

2016

Bioorganic & Medicinal Chemistry

221

172

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Daptomycin is a lipopeptide antibiotic produced by the soil bacterium Streptomyces roseosporus that is clinically used to treat severe infections with Grampositive bacteria. In this review, we discuss the mode of action of this important antibiotic. Although daptomycin is structurally related to amphomycin and similar lipopeptides that inhibit peptidoglycan biosynthesis, experimental studies have not produced clear evidence that daptomycin shares their action mechanism. Instead, the best characterized effect of daptomycin is the permeabilization and depolarization of the bacterial cell membrane. This activity, which can account for daptomycin's bactericidal effect, correlates with the level of phosphatidylglycerol (PG) in the membrane. Accordingly, reduced synthesis of PG or its increased conversion to lysyl-PG promotes bacterial resistance to daptomycin. While other resistance mechanisms suggest that daptomycin may indeed directly interfere with cell wall synthesis or cell division, such effects still await direct experimental confirmation. Daptomycin's complex structure and biosynthesis have hampered the analysis of its structure activity relationships. Novel methods of total synthesis, including a recent one that is carried out entirely on a solid phase, will enable a more thorough and systematic exploration of the sequence space.

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Section: Solution Structure Of Calcium-bound Daptomycinmentioning

confidence: 89%

Section: Calcium-induced Aggregation and Its Role In Daptomycin Delivmentioning

confidence: 92%

Section: Aggregation Of Free Daptomycin In Solutionmentioning

confidence: 99%

“…36 Some aggregation of apo-daptomycin would be expected to occur under these conditions. A preferred aqueous conformation for apo-daptomycin was also reported.…”

Section: Solution Structure Of Apo-daptomycinmentioning

confidence: 99%

Section: Solution Structure Of Calcium-bound Daptomycinmentioning

confidence: 99%

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The action mechanism of daptomycin

Taylor

Palmer

2016

Bioorganic & Medicinal Chemistry

221

172

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A well‐defined amphipathic conformation for the calcium‐free cyclic lipopeptide antibiotic, daptomycin, in aqueous solution

Rotondi

Gierasch

2005

Biopolymers

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Daptomycin is a 13-residue cyclic lipopeptide with Ca 2ϩ -dependent bactericidal activity against a variety of high-risk pathogens. Ring closure in daptomycin is via an ester linkage between the side chain of-free daptomycin is reported to lack a well-defined conformation (D. Jung, A. Rozek, M. Okron, and R. E. W. Hancock, Chemistry & Biology, 2004, Vol. 11, pp. 949-957) or is suggested to populate an alternate conformation (L.-J. Ball, C. M. Goult, J. A. Donarski, J. Micklefield, and V. Ramesh, Organic & Biomolecular Chemistry, 2004, Vol. 2, pp. 1872-1878 Contract grant sponsor: CUBIST Pharmaceuticals and NIH Contract grant number: GM27616 (NIH) *We dedicate this article to the memory of Murray Goodman, a bigger-than-life peptide chemist. He pursued the science of peptide design and synthesis, structure determination, and biological activity with passion. He showed by example how warmth and scientific zeal are contagious traits that engender international liaisons in the pursuit of common goals. He will be sorely missed.

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Manipulation of kynurenine pathway for enhanced daptomycin production in Streptomyces roseosporus

Liao

Wang

Liu

et al. 2013

Biotechnology Progress

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Daptomycin is a cyclic lipopeptide natural product produced by Stretptomyces roseosporus, displaying good bactericidal activity against a wide range of gram-positive pathogens. Daptomycin contains a 13 amino acid and kynurenine (Kyn) is essential for optimal activity of daptomycin. In this study, we characterized the Kyn pathway in S. roseosporus and investigated its role in supplying precursor for daptomycin biosynthesis. Two genes (dptJ and tdo) coding for tryptophan-2,3-dioxgenase existed in the chromosome. dptJ is located in the daptomycin biosynthetic gene cluster, while tdo is in other locus. Disruption of dptJ or tdo resulted in reduced yield by ∼50%. The introduction of an additional copy of dptJ but not tdo led to enhanced production of daptomycin by 110%. Furthermore, disruption of kyn encoding kynureninase showed improved daptomycin productivity by 30%. Our results demonstrated that the enhancement of Kyn supply through metabolic engineering approach is an efficient way to increase daptomycin production.

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NMR structure determination and calcium binding effects of lipopeptide antibiotic daptomycin

Cited by 93 publications

References 23 publications

The action mechanism of daptomycin

The action mechanism of daptomycin

A well‐defined amphipathic conformation for the calcium‐free cyclic lipopeptide antibiotic, daptomycin, in aqueous solution

Manipulation of kynurenine pathway for enhanced daptomycin production in Streptomyces roseosporus

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