scholarly journals Identification of novel mureidomycin analogues via rational activation of a cryptic gene cluster in Streptomyces roseosporus NRRL 15998

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Lingjuan Jiang ◽  
Lu Wang ◽  
Jihui Zhang ◽  
Hao Liu ◽  
Bin Hong ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Streptomyces Roseosporus

scholarly journals MS/MS-based networking and peptidogenomics guided genome mining revealed the stenothricin gene cluster in Streptomyces roseosporus

2013 ◽  
Vol 67 (1) ◽  
pp. 99-104 ◽  
Author(s):  
Wei-Ting Liu ◽  
Anne Lamsa ◽  
Weng Ruh Wong ◽  
Paul D Boudreau ◽  
Roland Kersten ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Genome Mining ◽  
Streptomyces Roseosporus

Daptomycin biosynthesis in Streptomyces roseosporus: cloning and analysis of the gene cluster and revision of peptide stereochemistry

Microbiology ◽  
2005 ◽  
Vol 151 (5) ◽  
pp. 1507-1523 ◽  
Author(s):  
Vivian Miao ◽  
Marie-Françoise Coëffet-LeGal ◽  
Paul Brian ◽  
Renee Brost ◽  
Julia Penn ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Gene Cluster ◽  
Binding Pocket ◽  
Biosynthetic Gene Cluster ◽  
Streptomyces Roseosporus ◽  
Cyclic Lipopeptide ◽  
Peptide Synthetase ◽  
Amino Acid Binding ◽  
Condensation Domain

Daptomycin is a 13 amino acid, cyclic lipopeptide produced by a non-ribosomal peptide synthetase (NRPS) mechanism in Streptomyces roseosporus. A 128 kb region of S. roseosporus DNA was cloned and verified by heterologous expression in Streptomyces lividans to contain the daptomycin biosynthetic gene cluster (dpt). The cloned region was completely sequenced and three genes (dptA, dptBC, dptD) encoding the three subunits of an NRPS were identified. The catalytic domains in the subunits, predicted to couple five, six or two amino acids, respectively, included a novel activation domain and amino-acid-binding pocket for incorporating the unusual amino acid l-kynurenine (Kyn), three types of condensation domains and an extra epimerase domain (E-domain) in the second module. Novel genes (dptE, dptF) whose products likely work in conjunction with a unique condensation domain to acylate the first amino acid, as well as other genes (dptI, dptJ) probably involved in supply of the non-proteinogenic amino acids l-3-methylglutamic acid and Kyn, were located next to the NRPS genes. The unexpected E-domain suggested that daptomycin would have d-Asn, rather than l-Asn, as originally assigned, and this was confirmed by comparing stereospecific synthetic peptides and the natural product both chemically and microbiologically.

scholarly journals Molecular Cloning and Physical Mapping of the Daptomycin Gene Cluster from Streptomyces roseosporus

1998 ◽  
Vol 180 (1) ◽  
pp. 143-151 ◽  
Author(s):  
Margaret A. Mchenney ◽  
Thomas J. Hosted ◽  
Bradley S. Dehoff ◽  
Paul R. Rosteck ◽  
Richard H. Baltz
Keyword(s):  
Molecular Cloning ◽  
Gene Cluster ◽  
Physical Mapping ◽  
Insertional Mutagenesis ◽  
Biosynthetic Gene Cluster ◽  
Biosynthetic Gene ◽  
Linear Chromosome ◽  
Coding Regions ◽  
Streptomyces Roseosporus ◽  
Peptide Synthetase

ABSTRACT The daptomycin biosynthetic gene cluster of Streptomyces roseosporus was analyzed by Tn5099 mutagenesis, molecular cloning, partial DNA sequencing, and insertional mutagenesis with cloned segments of DNA. The daptomycin biosynthetic gene cluster spans at least 50 kb and is located about 400 to 500 kb from one end of the ∼7,100-kb linear chromosome. We identified two peptide synthetase coding regions interrupted by a 10- to 20-kb region that may encode other functions in lipopeptide biosynthesis.

OMIC gene cluster evaluation amplifies the prognostic accuracy of the NETest

2020 ◽  
Author(s):  
Mark Kidd ◽  
Alexandra Kitz ◽  
Ignat Drozdov ◽  
Irvin Modlin
Keyword(s):  
Gene Cluster ◽  
Prognostic Accuracy ◽  
Cluster Evaluation

Anacyclamide D8P, a prenylated cyanobactin from a Sphaerospermopsis sp. cyanobacterium

2017 ◽  
Author(s):  
Joana Martins ◽  
Niina Leikoski ◽  
Matti Wahlsten ◽  
Joana Azevedo ◽  
Jorge Antunes ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Cyclic Peptides ◽  
Biosynthetic Gene Cluster ◽  
The Novel ◽  
Tyrosine Residue ◽  
Biosynthetic Gene ◽  
Post Translational Modification ◽  
Biological Assays ◽  
Mass Spectrometric Data ◽  
Spectrometric Data

Cyanobactins are a family of linear and cyclic peptides produced through the post-translational modification of short precursor peptides. Anacyclamides are macrocyclic cyanobactins with a highly diverse sequence that are common in the genus <i>Anabaena</i>. A mass spectrometry-based screening of potential cyanobactin producers led to the discovery of a new prenylated member of this family of compounds, anacyclamide D8P (<b>1</b>), from <i>Sphaerospermopsis</i> sp. LEGE 00249. The anacyclamide biosynthetic gene cluster (<i>acy</i>) encoding the novel macrocyclic prenylated cyanobactin, was sequenced. Heterologous expression of the acy gene cluster in <i>Escherichia</i> <i>coli</i> established the connection between genomic and mass spectrometric data. Unambiguous establishment of the type and site of prenylation required the full structural elucidation of <b>1</b> using Nuclear Magnetic Resonance (NMR), which demonstrated that a forward prenylation occurred on the tyrosine residue. Compound <b>1</b> was tested in pharmacologically or ecologically relevant biological assays and revealed moderate antimicrobial activity towards the fouling bacterium <i>Halomonas aquamarina</i> CECT 5000.<br>

Unzipping Natural Products: Improved Natural Product Structure Predictions by Ensemble Modeling and Fingerprint Matching

2018 ◽  
Author(s):  
William A. Shirley ◽  
Brian P. Kelley ◽  
Yohann Potier ◽  
John H. Koschwanez ◽  
Robert Bruccoleri ◽  
...  
Keyword(s):  
Natural Products ◽  
Open Source ◽  
Natural Product ◽  
Gene Cluster ◽  
Public Domain ◽  
Product Structure ◽  
Fingerprint Matching ◽  
Ensemble Modeling ◽  
Chemical Structures ◽  
Source Gene

This pre-print explores ensemble modeling of natural product targets to match chemical structures to precursors found in large open-source gene cluster repository antiSMASH. Commentary on method, effectiveness, and limitations are enclosed. All structures are public domain molecules and have been reviewed for release.

Synthesis and Reactivity of Precolibactin 886

2019 ◽  
Author(s):  
Seth Herzon ◽  
Alan R. Healy ◽  
kevin wernke ◽  
Chung Sub Kim ◽  
Nicholas Lees ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gene Cluster ◽  
Amino Alcohol ◽  
Biomimetic Synthesis ◽  
Cross Linking ◽  
E Coli ◽  
Hplc Purification ◽  
Structural Assignment ◽  
Biosynthetic Precursor ◽  
Double Oxidation

<div>The clb gene cluster encodes the biosynthesis of metabolites known as precolibactins and colibactins. The clb pathway is found in gut commensal E. coli, and clb metabolites are thought to initiate colorectal cancer via DNA cross-linking. Precolibactin 886 (1) is one of the most complex isolated clb metabolites; it contains a 15-atom macrocycle and an unusual 5-hydroxy-3-oxazoline ring. Here we report confirmation of the structural assignment via a biomimetic synthesis of precolibactin 886 (1) proceeding through the amino alcohol 9. Double oxidation of 9 afforded the unstable α-ketoimine 2 which underwent macrocyclization to precolibactin 886 (1) upon HPLC purification (3% from 9). Studies of the putative precolibactin 886 (1) biosynthetic precursor 2, the model α-ketoimine 25, and the α-dicarbonyl 26 revealed that these compounds are susceptible to nucleophilic rupture of the C36–C37 bond. Moreover, cleavage of 2 produces other known clb metabolites or biosynthetic intermediates. This unexpected reactivity explains the difficulties in isolating full clb metabolites and accounts for the structure of a recently identified colibactin–adenine adduct. The colibactin peptidase ClbP deacylates synthetic precolibactin 886 (1) to form a non-genotoxic pyridone, suggesting precolibactin 886 (1) lies off-path of the major biosynthetic route.</div>

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