Biosynthesis of lasalocid. III. Isolation and structure determination of four homologs of lasalocid A.

Jw, Westley; BENZ, W.; Donahue, John J.; Rh, Evans; Cg, Scott; Stempel, Arthur; Berger, Jacob

doi:10.7164/antibiotics.27.744

Cited by 30 publications

(9 citation statements)

References 1 publication

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“…A) Wild‐type S. lasaliensis (total ion current). The peak at 16.54 corresponds to a mixture of lasalocid B, lasalocid C and lasalocid D ( m / z 605 [ M +H] + ), minor products formed through the incorporation of an additional butyrate extender unit in place of propionate 47. B) Wild‐type S. lasaliensis (selection for m / z 591 [ M +H] + ).…”

Section: Resultsmentioning

confidence: 99%

Analysis of Specific Mutants in the Lasalocid Gene Cluster: Evidence for Enzymatic Catalysis of a Disfavoured Polyether Ring Closure

et al. 2008

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Lasalocid is a highly atypical polyether ionophoric antibiotic, firstly because it contains a type of aromatic ring normally associated with fungal polyketides, and secondly because the formation of its tetrahydropyran ring appears to contravene Baldwin's rules, which predict the kinetically preferred routes for cyclisation reactions in organic chemistry. The lasalocid biosynthetic gene cluster has been cloned from Streptomyces lasaliensis, and the las locus (73,533 bp) was found to contain seven modular polyketide synthase (PKS) genes, including all the activities necessary for the synthesis of the aromatic moiety. Specific deletion from the gene cluster of the flanking lasC gene, which is predicted to encode a flavin-linked epoxidase, abolished production both of lasalocid and of the minor cometabolite iso-lasalocid without leading to accumulation of an identifiable intermediate; this suggests that oxidative cyclisation to form the polyether rings takes place on the PKS before release of the full-length polyketide product. Meanwhile, a mutant in which the adjacent epoxide hydrolase lasB had been deleted produced iso-lasalocid only. Iso-lasalocid differs from lasalocid in the replacement of the tetrahydropyran ring by a tetrohydrofuran ring and represents the kinetically favoured product of cyclisation. The LasB epoxide hydrolase is therefore directly implicated in control of the stereochemical course of polyether ring formation during lasalocid biosynthesis.

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Section: Resultsmentioning

confidence: 99%

Analysis of Specific Mutants in the Lasalocid Gene Cluster: Evidence for Enzymatic Catalysis of a Disfavoured Polyether Ring Closure

et al. 2008

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“…This may be reasonable, since the biosynthesis of lasalocid required more than three moles of ethylmalonyl-CoA. This powerful supply system guarantees a sufficient amount of ethylmalonyl-CoA and may contribute to the production of lasalocids B-E, 41) in which the pendant methyl substituent is replaced by an ethyl group at various positions.…”

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confidence: 99%

Identification of a Gene Cluster of Polyether Antibiotic Lasalocid fromStreptomyces lasaliensis

Migita

Watanabe

Hirose

et al. 2009

Bioscience, Biotechnology, and Biochemistry

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“…With this innovative method in hands, the authors explored the synthetic applicability in the preparation of a core unit from lasalocid A (124), a known antibiotic drug [194] that, along with its four analogues 120-123 (Scheme 37A), were extracted from Streptomyces lasaliensis cultures [195]. The synthesis succeeded in five steps, each one of them in good yields, including the cobalt-catalyzed C-H bond addition (Scheme 37D).…”

Section: Cobalt-catalyzed C-h Activationmentioning

confidence: 99%

“…In this work, a deoxy-arylation process of azoles led to the formation of several arylated products in moderate to good yields, including the important alkaloids texamine (193) [275] and uguenenazole (194) [276] (Scheme 60B). The authors applied the same developed methodology in a late-stage study to modify the derivative of the naturally occurring compounds estrone triflate (195) [277] and quinine triflate (196) [278] (Scheme 60C).…”

Section: Nickel-catalyzed C-h Activationmentioning

confidence: 99%

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

Carvalho¹,

Miranda²,

Nunes³

et al. 2021

Beilstein J. Org. Chem.

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Several valuable biologically active molecules can be obtained through C–H activation processes. However, the use of expensive and not readily accessible catalysts complicates the process of pharmacological application of these compounds. A plausible way to overcome this issue is developing and using cheaper, more accessible, and equally effective catalysts. First-row transition (3d) metals have shown to be important catalysts in this matter. This review summarizes the use of 3d metal catalysts in C–H activation processes to obtain potentially (or proved) biologically active compounds.

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Biosynthesis of lasalocid. III. Isolation and structure determination of four homologs of lasalocid A.

Cited by 30 publications

References 1 publication

Analysis of Specific Mutants in the Lasalocid Gene Cluster: Evidence for Enzymatic Catalysis of a Disfavoured Polyether Ring Closure

Analysis of Specific Mutants in the Lasalocid Gene Cluster: Evidence for Enzymatic Catalysis of a Disfavoured Polyether Ring Closure

Identification of a Gene Cluster of Polyether Antibiotic Lasalocid fromStreptomyces lasaliensis

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

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