scholarly journals Structural and Functional Insights into a Peptide Bond-Forming Bidomain from a Nonribosomal Peptide Synthetase

Structure ◽  
2007 ◽  
Vol 15 (7) ◽  
pp. 781-792 ◽  
Author(s):  
Stefan A. Samel ◽  
Georg Schoenafinger ◽  
Thomas A. Knappe ◽  
Mohamed A. Marahiel ◽  
Lars-Oliver Essen
Keyword(s):  
Peptide Bond ◽  
Nonribosomal Peptide Synthetase ◽  
Nonribosomal Peptide ◽  
Bond Forming ◽  
Peptide Synthetase

scholarly journals tRNA-Dependent Aminoacylation of an Amino Sugar Intermediate in the Biosynthesis of a Streptothricin-Related Antibiotic

2016 ◽  
Vol 82 (12) ◽  
pp. 3640-3648 ◽  
Author(s):  
Chitose Maruyama ◽  
Haruka Niikura ◽  
Miho Izumikawa ◽  
Junko Hashimoto ◽  
Kazuo Shin-ya ◽  
...  
Keyword(s):  
Structural Diversity ◽  
Amino Sugar ◽  
Peptide Bond ◽  
Nonribosomal Peptide Synthetase ◽  
Side Chain ◽  
Content Type ◽  
Bond Forming ◽  
Peptide Synthetase ◽  
Related Compounds ◽  
Distinct Peptide

ABSTRACTThe antibiotic streptothricin (ST) possesses an amino sugar bound to anl-β-lysine (β-Lys) residue via a peptide bond. The peptide bond formation has been shown to be catalyzed by a nonribosomal peptide synthetase (NRPS) during ST biosynthesis. The focus of this study is the closely related ST analogue BD-12, which carries a glycine-derived side chain rather than a β-Lys residue. Here, inStreptomyces luteocolorNBRC13826, we describe our biosynthetic studies of BD-12, which revealed that the peptide bond between the amino sugar and the glycine residue is catalyzed by a Fem-like enzyme (Orf11) in a tRNA-dependent manner rather than by an NRPS. Although there have been several reports of peptide bond-forming tRNA-dependent enzymes, to our knowledge, Orf11 is the first enzyme that can accept an amino sugar as a substrate. Our findings clearly demonstrate that the structural diversity of the side chains of ST-type compounds in nature is generated in an unusual manner via two distinct peptide bond-forming mechanisms. Moreover, the identification and functional analysis of Orf11 resulted in not only the production of new ST-related compounds, but also the provision of new insights into the structure-activity relationship of the ST-related antibiotics.IMPORTANCEThe antibiotic streptothricin (ST) possesses an amino sugar bound to anl-β-lysine (β-Lys) side chain via a peptide bond formed by a nonribosomal peptide synthetase (NRPS). BD-12, an analogue of ST, carries a glycine-derived side chain rather than β-Lys, and here, we describe the BD-12-biosynthetic gene cluster fromStreptomycesluteocolorNBRC13826, which contains theorf11gene encoding a novel tRNA-dependent peptide bond-forming enzyme. The unique Fem-like enzyme (Orf11) accepts the amino sugar as a substrate and mediates the peptide formation between the amino sugar intermediate and glycine. Our studies demonstrate that the structural diversity of the side chains of ST-related compounds in nature is generated via two distinct peptide bond-forming mechanisms.

scholarly journals Biosynthesis of Novel Pyoverdines by Domain Substitution in a Nonribosomal Peptide Synthetase of Pseudomonas aeruginosa

2014 ◽  
Vol 80 (18) ◽  
pp. 5723-5731 ◽  
Author(s):  
Mark J. Calcott ◽  
Jeremy G. Owen ◽  
Iain L. Lamont ◽  
David F. Ackerley
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Peptide Bond ◽  
Nonribosomal Peptide Synthetase ◽  
Nonribosomal Peptide ◽  
Content Type ◽  
Threonine Residue ◽  
Peptide Synthetase ◽  
A Domains ◽  
High Yields ◽  
Acid Substrate

ABSTRACTPyoverdine is a fluorescent nonribosomal peptide siderophore made by fluorescent pseudomonads. ThePseudomonas aeruginosanonribosomal peptide synthetase (NRPS) PvdD contains two modules that each incorporate anl-threonine residue at the C-terminal end of pyoverdine. In an attempt to generate modified pyoverdine peptides, we substituted alternative-substrate-specifying adenylation (A) and peptide bond-catalyzing condensation (C) domains into the second module of PvdD. When just the A domain was substituted, the resulting strains produced only wild-type pyoverdine—at high levels if the introduced A domain specified threonine or at trace levels otherwise. The high levels of pyoverdine synthesis observed whenever the introduced A domain specified threonine indicated that these nonnative A domains were able to communicate effectively with the PvdD C domain. Moreover, the unexpected observation that non-threonine-specifying A domains nevertheless incorporated threonine into pyoverdine suggests that the native PvdD C domain exhibited stronger selectivity than these A domains for the incorporated amino acid substrate (i.e., misactivation of a threonine residue by the introduced A domains was more frequent than misincorporation of a nonthreonine residue by the PvdD C domain). In contrast, substitution of both the C and A domains of PvdD generated high yields of rationally modified pyoverdines in two instances, these pyoverdines having either a lysine or a serine residue in place of the terminal threonine. However, C-A domain substitution more commonly yielded a truncated peptide product, likely due to stalling of synthesis on a nonfunctional recombinant NRPS template.

scholarly journals Draft Genome Sequence of Saccharomonospora sp. Strain LRS4.154, a Moderately Halophilic Actinobacterium with the Biotechnologically Relevant Polyketide Synthase and Nonribosomal Peptide Synthetase Systems

2017 ◽  
Vol 5 (21) ◽  
Author(s):  
Scarlett Alonso-Carmona ◽  
Blanca Vera-Gargallo ◽  
Rafael R. de la Haba ◽  
Antonio Ventosa ◽  
Horacio Sandoval-Trujillo ◽  
...  
Keyword(s):  
Genome Sequence ◽  
Polyketide Synthase ◽  
Draft Genome ◽  
Nonribosomal Peptide Synthetase ◽  
Open Reading Frames ◽  
Draft Genome Sequence ◽  
Nonribosomal Peptide ◽  
Moderately Halophilic ◽  
Peptide Synthetase ◽  
Reading Frames

ABSTRACT The draft genome sequence of Saccharomonospora sp. strain LRS4.154, a moderately halophilic actinobacterium, has been determined. The genome has 4,860,108 bp, a G+C content of 71.0%, and 4,525 open reading frames (ORFs). The clusters of PKS and NRPS genes, responsible for the biosynthesis of a large number of biomolecules, were identified in the genome.

Engineered Nonribosomal Peptide Synthetase Shows Opposite Amino Acid Loading and Condensation Specificity

ACS Catalysis ◽  
2021 ◽  
pp. 8692-8700
Author(s):  
Aleksa Stanišić ◽  
Annika Hüsken ◽  
Philipp Stephan ◽  
David L. Niquille ◽  
Jochen Reinstein ◽  
...  
Keyword(s):  
Amino Acid ◽  
Nonribosomal Peptide Synthetase ◽  
Nonribosomal Peptide ◽  
Peptide Synthetase ◽  
Acid Loading

scholarly journals Antimicrobials Inspired by Nonribosomal Peptide Synthetase Gene Clusters

2017 ◽  
Vol 139 (4) ◽  
pp. 1404-1407 ◽  
Author(s):  
Xavier Vila-Farres ◽  
John Chu ◽  
Daigo Inoyama ◽  
Melinda A. Ternei ◽  
Christophe Lemetre ◽  
...  
Keyword(s):  
Gene Clusters ◽  
Nonribosomal Peptide Synthetase ◽  
Nonribosomal Peptide ◽  
Peptide Synthetase
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