Structure determination of lysobactin, a macrocyclic peptide lactone antibiotic

Tymiak, Adrienne A.; McCormick, Terrence J.; Unger, Steve

doi:10.1021/jo00266a029

Cited by 90 publications

(58 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These traits include production of extracellular degradative enzymes, such as chitinases, glucanases, and proteases, as well as production of antibiotic compounds (5,20,36,37). Mutations in the clp gene had a global effect on a variety of L. enzymogenes phenotypes, including significant re- (44) demonstrated that chitinases purified from culture filtrates enhanced biocontrol of bipolaris leaf spot by strain C3.…”

Section: Discussionmentioning

confidence: 99%

A clp Gene Homologue Belonging to the Crp Gene Family Globally Regulates Lytic Enzyme Production, Antimicrobial Activity, and Biological Control Activity Expressed by Lysobacter enzymogenes Strain C3

Kobayashi

Reedy

Palumbo

et al. 2005

Appl Environ Microbiol

View full text Add to dashboard Cite

Lysobacter enzymogenes strain C3, a biological control agent for plant diseases, produces multiple extracellular hydrolytic enzymes and displays antimicrobial activity against various fungal and oomycetous species. However, little is known about the regulation of these enzymes or their roles in antimicrobial activity and biocontrol. A study was undertaken to identify mutants of strain C3 affected in extracellular enzyme production and to evaluate their biocontrol efficacy. A single mini-Tn5-lacZ 1 -cat transposon mutant of L. enzymogenes strain C3 that was globally affected in a variety of phenotypes was isolated. In this mutant, 5E4, the activities of several extracellular lytic enzymes, gliding motility, and in vitro antimicrobial activity were reduced. Characterization of 5E4 indicated that the transposon inserted in a clp gene homologue belonging to the Crp gene family of regulators. Immediately downstream was a second open reading frame similar to that encoding acetyltransferases belonging to the Gcn5-related N-acetyltransferase superfamily, which reverse transcription-PCR confirmed was cotranscribed with clp. Chromosomal deletion mutants with mutations in clp and between clp and the acetyltransferase gene verified the 5E4 mutant phenotype. The clp gene was chromosomally inserted in mutant 5E4, resulting in complemented strain P1. All mutant phenotypes were restored in P1, although the gliding motility was observed to be excessive compared with that of the wild-type strain. clp mutant strains were significantly affected in biological control of pythium damping-off of sugar beet and bipolaris leaf spot of tall fescue, which was partially or fully restored in the complemented strain P1. These results indicate that clp is a global regulatory gene that controls biocontrol traits expressed by L. enzymogenes C3.

show abstract

Section: Discussionmentioning

confidence: 99%

A clp Gene Homologue Belonging to the Crp Gene Family Globally Regulates Lytic Enzyme Production, Antimicrobial Activity, and Biological Control Activity Expressed by Lysobacter enzymogenes Strain C3

Kobayashi

Reedy

Palumbo

et al. 2005

Appl Environ Microbiol

View full text Add to dashboard Cite

show abstract

“…(2S,3R)-3-hydroxyleucine is a promising material for the preparation of certain cyclic depsipeptides, which function as platelet aggregation inhibitors, and is also a component of the antibiotic lysobactin. 35,36) In addition, SadA has potential as a catalyst of stereoselective hydroxylation to produce L-threo-3,4-dihydroxyphenylserine (L-DOPS, Droxidopa), which is a psychoactive drug and synthetic amino acid precursor that acts as a prodrug to neurotransmitters norepinephrine and epinephrine. [37][38][39] The SadA structure provides the mechanistic basis for the stereoselective reaction of NSLeu to make the expansion of substrate specificity possible.…”

Section: Stereoselective Catalytic Mechanism Of Dioxygenase and mentioning

confidence: 99%

Structural analysis of enzymes used for bioindustry and bioremediation

Tanokura

Miyakawa

Guan

et al. 2015

Bioscience, Biotechnology, and Biochemistry

View full text Add to dashboard Cite

Microbial enzymes have been widely applied in the large-scale, bioindustrial manufacture of food products and pharmaceuticals due to their high substrate specificity and stereoselectivity, and their effectiveness under mild conditions with low environmental burden. At the same time, bioremedial techniques using microbial enzymes have been developed to solve the problem of industrial waste, particularly with respect to persistent chemicals and toxic substances. And finally, structural studies of these enzymes have revealed the mechanistic basis of enzymatic reactions, including the stereoselectivity and binding specificity of substrates and cofactors. The obtained structural insights are useful not only to deepen our understanding of enzymes with potential bioindustrial and/or bioremedial application, but also for the functional improvement of enzymes through rational protein engineering. This review shows the structural bases for various types of enzymatic reactions, including the substrate specificity accompanying cofactor-controlled and kinetic mechanisms.

show abstract

“…On the other hand, the lactone bond in lysobactin is prone to hydrolysis. [34] However, its stable and highly potent amide analogue has been prepared. [35] The total syntheses of lysobactins have recently been highlighted.…”

Section: Lysobactin/katanosinmentioning

confidence: 99%

Recent Progress in the Discovery of Macrocyclic Compounds as Potential Anti-Infective Therapeutics

Obrecht¹,

Robinson²,

Bernardini

et al. 2009

CMC

View full text Add to dashboard Cite

O (2009Recent progress in the discovery of macrocyclic compounds as potential anti-infective therapeutics AbstractNovel therapeutic strategies are urgently needed for the treatment of serious diseases caused by viral, bacterial and parasitic infections, because currently used drugs are facing the problem of rapidly emerging resistance. There is also an urgent need for agents that act on novel pathogen-specific targets, in order to expand the repertoire of possible therapies. The high throughput screening of diverse small molecule compound libraries has provided only a limited number of new lead series, and the number of compounds acting on novel targets is even smaller. Natural product screening has traditionally been very successful in the anti-infective area. Several successful drugs on the market as well as other compounds in clinical development are derived from natural products. Amongst these, many are macrocyclic compounds in the 1-2 kDa size range. This review will describe recent advances and novel drug discovery approaches in the anti-infective area, focusing on synthetic and natural macrocyclic compounds for which in vivo proof of concept has been established. The review will also highlight the Protein Epitope Mimetics (PEM) technology as a novel tool in the drug discovery process. Here the structures of naturally occurring antimicrobial and antiviral peptides and proteins are used as starting points to generate novel macrocyclic mimetics, which can be produced and optimized efficiently by combinatorial synthetic methods. Several recent examples highlight the great potential of the PEM approach in the discovery of new anti-infective agents. Abstract:Novel therapeutic strategies are urgently needed for the treatment of serious

show abstract

Structure determination of lysobactin, a macrocyclic peptide lactone antibiotic

Cited by 90 publications

References 7 publications

A clp Gene Homologue Belonging to the Crp Gene Family Globally Regulates Lytic Enzyme Production, Antimicrobial Activity, and Biological Control Activity Expressed by Lysobacter enzymogenes Strain C3

A clp Gene Homologue Belonging to the Crp Gene Family Globally Regulates Lytic Enzyme Production, Antimicrobial Activity, and Biological Control Activity Expressed by Lysobacter enzymogenes Strain C3

Structural analysis of enzymes used for bioindustry and bioremediation

Recent Progress in the Discovery of Macrocyclic Compounds as Potential Anti-Infective Therapeutics

Contact Info

Product

Resources

About