scholarly journals Methyltransferases of gentamicin biosynthesis

2018 ◽  
Vol 115 (6) ◽  
pp. 1340-1345 ◽  
Author(s):  
Sicong Li ◽  
Junhong Guo ◽  
Anna Reva ◽  
Fanglu Huang ◽  
Binbin Xiong ◽  
...  
Keyword(s):  
Gene Deletion ◽  
Biosynthetic Gene Cluster ◽  
Methylation Pattern ◽  
Whole Genome Sequence ◽  
Specific Gene ◽  
Biosynthetic Gene ◽  
Biosynthetic Enzyme ◽  
Micromonospora Echinospora ◽  
Therapeutic Properties ◽  
C Complex

Gentamicin C complex from Micromonospora echinospora remains a globally important antibiotic, and there is revived interest in the semisynthesis of analogs that might show improved therapeutic properties. The complex consists of five components differing in their methylation pattern at one or more sites in the molecule. We show here, using specific gene deletion and chemical complementation, that the gentamicin pathway up to the branch point is defined by the selectivity of the methyltransferases GenN, GenD1, and GenK. Unexpectedly, they comprise a methylation network in which early intermediates are ectopically modified. Using whole-genome sequence, we have also discovered the terminal 6′-N-methyltransfer required to produce gentamicin C2b from C1a or gentamicin C1 from C2, an example of an essential biosynthetic enzyme being located not in the biosynthetic gene cluster but far removed on the chromosome. These findings fully account for the methylation pattern in gentamicins and open the way to production of individual gentamicins by fermentation, as starting materials for semisynthesis.

scholarly journals Organization of the biosynthetic gene cluster in Streptomyces sp. DSM 4137 for the novel neuroprotectant polyketide meridamycin

Microbiology ◽  
2006 ◽  
Vol 152 (12) ◽  
pp. 3507-3515 ◽  
Author(s):  
Yuhui Sun ◽  
Hui Hong ◽  
Markiyan Samborskyy ◽  
Tatiana Mironenko ◽  
Peter F. Leadlay ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
Gene Deletion ◽  
Polyketide Synthase ◽  
Biosynthetic Gene Cluster ◽  
Specific Gene ◽  
The Novel ◽  
Biosynthetic Gene ◽  
Modular Polyketide Synthase

Meridamycin is a non-immunosuppressant, FKBP-binding macrocyclic polyketide, which has major potential as a neuroprotectant in a range of neurodegenerative disorders including dementia, Parkinson's disease and ischaemic stroke. A biosynthetic cluster predicted to encode biosynthesis of meridamycin was cloned from the prolific secondary-metabolite-producing strain Streptomyces sp. DSM 4137, not previously known to produce this compound, and specific gene deletion was used to confirm the role of this cluster in the biosynthesis of meridamycin. The meridamycin modular polyketide synthase consists of 14 extension modules distributed between three giant multienzyme proteins. The terminal module is flanked by a highly unusual cytochrome P450-like domain. The characterization of the meridamycin biosynthetic locus in this readily manipulated streptomycete species opens the way to the engineering of new, altered meridamycins of potential therapeutic importance.

scholarly journals New Insights into the Genetic Organization of the FK228 Biosynthetic Gene Cluster inChromobacterium violaceumNo. 968

2010 ◽  
Vol 77 (4) ◽  
pp. 1508-1511 ◽  
Author(s):  
Vishwakanth Y. Potharla ◽  
Shane R. Wesener ◽  
Yi-Qiang Cheng
Keyword(s):  
Natural Product ◽  
Gene Cluster ◽  
Gene Deletion ◽  
Regulatory Gene ◽  
Biosynthetic Gene Cluster ◽  
Transcriptional Analysis ◽  
Biosynthetic Gene ◽  
Genetic Organization

ABSTRACTThe biosynthetic gene cluster of FK228, an FDA-approved anticancer natural product, was identified and sequenced previously. The genetic organization of this gene cluster has now been delineated through systematic gene deletion and transcriptional analysis. As a result, the gene cluster is redefined to contain 12 genes:depAthroughdepJ,depM, and a newly identified pathway regulatory gene,depR.

Biosynthesis of the uridine-derived nucleoside antibiotic A-94964: identification and characterization of the biosynthetic gene cluster provide insight into the biosynthetic pathway

2019 ◽  
Vol 17 (3) ◽  
pp. 461-466 ◽  
Author(s):  
Taro Shiraishi ◽  
Makoto Nishiyama ◽  
Tomohisa Kuzuyama
Keyword(s):  
Gene Cluster ◽  
In Silico ◽  
Biosynthetic Pathway ◽  
Gene Deletion ◽  
Biosynthetic Gene Cluster ◽  
Biosynthetic Gene ◽  
Identification And Characterization ◽  
Insight Into

The biosynthetic pathway of the uridine-derived nucleoside antibiotic A-94964 was proposed via in silico analysis coupled with gene deletion experiments.

scholarly journals Comparative Genomics among Closely Related Streptomyces Strains Revealed Specialized Metabolite Biosynthetic Gene Cluster Diversity

Antibiotics ◽  
2018 ◽  
Vol 7 (4) ◽  
pp. 86 ◽  
Author(s):  
Cláudia Vicente ◽  
Annabelle Thibessard ◽  
Jean-Noël Lorenzi ◽  
Mabrouka Benhadj ◽  
Laurence Hôtel ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Sequence Data ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Core Gene ◽  
Chemical Diversity ◽  
Specific Gene ◽  
Biosynthetic Gene ◽  
Single Strain ◽  
Specialized Metabolites

Specialized metabolites are of great interest due to their possible industrial and clinical applications. The increasing number of antimicrobial resistant infectious agents is a major health threat and therefore, the discovery of chemical diversity and new antimicrobials is crucial. Extensive genomic data from Streptomyces spp. confirm their production potential and great importance. Genome sequencing of the same species strains indicates that specialized metabolite biosynthetic gene cluster (SMBGC) diversity is not exhausted, and instead, a pool of novel specialized metabolites still exists. Here, we analyze the genome sequence data from six phylogenetically close Streptomyces strains. The results reveal that the closer strains are phylogenetically, the number of shared gene clusters is higher. Eight specialized metabolites comprise the core metabolome, although some strains have only six core gene clusters. The number of conserved gene clusters common between the isolated strains and their closest phylogenetic counterparts varies from nine to 23 SMBGCs. However, the analysis of these phylogenetic relationships is not affected by the acquisition of gene clusters, probably by horizontal gene transfer events, as each strain also harbors strain-specific SMBGCs. Between one and 15 strain-specific gene clusters were identified, of which up to six gene clusters in a single strain are unknown and have no identifiable orthologs in other species, attesting to the existing SMBGC novelty at the strain level.

scholarly journals Identification of a Biosynthetic Gene Cluster Responsible for the Production of a New Pyrrolopyrimidine Natural Product—Huimycin

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1074
Author(s):  
Hui Shuai ◽  
Maksym Myronovskyi ◽  
Suvd Nadmid ◽  
Andriy Luzhetskyy
Keyword(s):  
Gene Cluster ◽  
Gene Deletion ◽  
Biological Activities ◽  
Biosynthetic Gene Cluster ◽  
Resonance Spectroscopy ◽  
Important Class ◽  
Biosynthetic Gene ◽  
Heterologous Host ◽  
Streptomyces Albus ◽  
Actinomycete Strain

Pyrrolopyrimidines are an important class of natural products with a broad spectrum of biological activities, including antibacterial, antifungal, antiviral, anticancer or anti-inflammatory. Here, we present the identification of a biosynthetic gene cluster from the rare actinomycete strain Kutzneria albida DSM 43870, which leads to the production of huimycin, a new member of the pyrrolopyrimidine family of compounds. The huimycin gene cluster was successfully expressed in the heterologous host strain Streptomyces albus Del14. The compound was purified, and its structure was elucidated by means of nuclear magnetic resonance spectroscopy. The minimal huimycin gene cluster was identified through sequence analysis and a series of gene deletion experiments. A model for huimycin biosynthesis is also proposed in this paper.

scholarly journals The expansive library of jadomycins

2018 ◽  
Vol 96 (6) ◽  
pp. 495-501 ◽  
Author(s):  
Jeanna M. MacLeod ◽  
Stephanie M. Forget ◽  
David L. Jakeman
Keyword(s):  
Amino Acids ◽  
Natural Products ◽  
Amino Acid ◽  
Heterologous Expression ◽  
Gene Cluster ◽  
Gene Deletion ◽  
Biosynthetic Gene Cluster ◽  
Biosynthetic Gene ◽  
Synthetic Derivatives ◽  
Subsequent Identification

The jadomycin family of natural products was discovered from Streptomyces venezuelae ISP5230 in the 1990s. Subsequent identification of the biosynthetic gene cluster along with synthetic efforts established that incorporation of an amino acid into the polyaromatic angucycline core occurs non-enzymatically. Over two decades, the precursor-directed biosynthetic potential of the jadomycins has been heavily exploited, generating a library exceeding 70 compounds. This review compiles the jadomycins that have been isolated and characterized to date; these include jadomycins incorporating proteinogenic and non-proteinogenic amino acids, semi-synthetic derivatives, biosynthetic shunt products, compounds isolated in structural gene deletion studies, and deoxysugar sugar variant jadomycins produced by deletion or heterologous expression of sugar biosynthetic genes.

scholarly journals Whole-genome sequence of a novel, mangrove-derived streptomycete, Streptomyces malaysiense strain MUSC 136T

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Hooi-Leng Ser ◽  
Wen-Si Tan ◽  
Wai-Fong Yin ◽  
Kok-Gan Chan ◽  
Learn-Han Lee
Keyword(s):  
Genome Sequence ◽  
Mangrove Forest ◽  
Streptomyces Griseus ◽  
Prediction Method ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters

Since the discovery of streptomycin from Streptomyces griseus in the early 1940s, streptomycetes from various environments have been studied thoroughly for the ability to produce bioactive compounds including antibacterial, antioxidant, anticancer, antifungal as well as immunomodulatory properties. Previously identified as a novel strain from a mangrove forest in Malaysia, Streptomyces malaysiense MUSC 136T was selected for genome sequencing to explore its genomic potential. The genomic size comprises of 7,963,326 bp with a G+C content of 72.2% and a total of 6,614 proteincoding genes. As an attempt to investigate the types of biosynthetic gene cluster present in the MUSC 136T, the whole genome sequence was analyzed with a bioinformatics tool, antibiotics & Secondary Metabolite Analysis Shell (antiSMASH). Using the “strict” prediction method, a total of seven biosynthetic gene clusters which displayed similarity of more than 80% to known gene clusters including ectoine, geosmin as well as desferrioxamine. Apart from emphasizing the importance of streptomycetes from unique environments like mangrove forest, the current study serves as a foundation for future studies on the role of specific genes present in biosynthetic gene clusters which enables the exploitation of MUSC 136T to synthesize important and valuable compounds.

Examination of the dynamics of global DNA methylation pattern establishment during spermatogenesiss

2007 ◽  
Vol 30 (4) ◽  
pp. 90
Author(s):  
Kirsten Niles ◽  
Sophie La Salle ◽  
Christopher Oakes ◽  
Jacquetta Trasler
Keyword(s):  
Dna Methylation ◽  
Germ Cell ◽  
Germ Cells ◽  
Epigenetic Modification ◽  
Methylation Pattern ◽  
Chromosome 9 ◽  
Specific Gene ◽  
Global Methylation ◽  
Dna Methylation Pattern ◽  
Methylation Patterns

Background: DNA methylation is an epigenetic modification involved in gene expression, genome stability, and genomic imprinting. In the male, methylation patterns are initially erased in primordial germ cells (PGCs) as they enter the gonadal ridge; methylation patterns are then acquired on CpG dinucleotides during gametogenesis. Correct pattern establishment is essential for normal spermatogenesis. To date, the characterization and timing of methylation pattern acquisition in PGCs has been described using a limited number of specific gene loci. This study aimed to describe DNA methylation pattern establishment dynamics during male gametogenesis through global methylation profiling techniques in a mouse model. Methods: Using a chromosome based approach, primers were designed for 24 regions spanning chromosome 9; intergenic, non-repeat, non-CpG island sequences were chosen for study based on previous evidence that these types of sequences are targets for testis-specific methylation events. The percent methylation was determined in each region by quantitative analysis of DNA methylation using real-time PCR (qAMP). The germ cell-specific pattern was determined by comparing methylation between spermatozoa and liver. To examine methylation in developing germ cells, spermatogonia from 2 day- and 6 day-old Oct4-GFP (green fluorescent protein) mice were isolated using fluorescence activated cell sorting. Results: As compared to liver, four loci were hypomethylated and five loci were hypermethylated in spermatozoa, supporting previous results indicating a unique methylation pattern in male germ cells. Only one region was hypomethylated and no regions were hypermethylated in day 6 spermatogonia as compared to mature spermatozoa, signifying that the bulk of DNA methylation is established prior to type A spermatogonia. The methylation in day 2 spermatogonia, germ cells that are just commencing mitosis, revealed differences of 15-20% compared to day 6 spermatogonia at five regions indicating that the most crucial phase of DNA methylation acquisition occurs prenatally. Conclusion: Together, these studies provide further evidence that germ cell methylation patterns differ from those in somatic tissues and suggest that much of methylation at intergenic sites is acquired during prenatal germ cell development. (Supported by CIHR)

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>

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