scholarly journals Utilization of the Methoxymalonyl-Acyl Carrier Protein Biosynthesis Locus for Cloning the Oxazolomycin Biosynthetic Gene Cluster from Streptomyces albus JA3453

2006 ◽  
Vol 188 (11) ◽  
pp. 4142-4147 ◽  
Author(s):  
Chunhua Zhao ◽  
Jianhua Ju ◽  
Steven D. Christenson ◽  
Wyatt C. Smith ◽  
Danfeng Song ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Acyl Carrier Protein ◽  
Protein Biosynthesis ◽  
Biosynthetic Gene Cluster ◽  
Carrier Protein ◽  
Biosynthetic Gene ◽  
Degenerate Primers ◽  
Streptomyces Albus ◽  
Genes Encoding ◽  
Antiviral Activities

ABSTRACT Oxazolomycin (OZM), a hybrid peptide-polyketide antibiotic, exhibits potent antitumor and antiviral activities. Using degenerate primers to clone genes encoding methoxymalonyl-acyl carrier protein (ACP) biosynthesis as probes, a 135-kb DNA region from Streptomyces albus JA3453 was cloned and found to cover the entire OZM biosynthetic gene cluster. The involvement of the cloned genes in OZM biosynthesis was confirmed by deletion of a 12-kb DNA fragment containing six genes for methoxymalonyl-ACP biosynthesis from the specific region of the chromosome, as well as deletion of the ozmC gene within this region, to generate OZM-nonproducing mutants.

scholarly journals Utilization of the Methoxymalonyl-Acyl Carrier Protein Biosynthesis Locus for Cloning of the Tautomycin Biosynthetic Gene Cluster from Streptomyces spiroverticillatus

2006 ◽  
Vol 188 (11) ◽  
pp. 4148-4152 ◽  
Author(s):  
Wenli Li ◽  
Jianhua Ju ◽  
Hiroyuki Osada ◽  
Ben Shen
Keyword(s):  
Gene Cluster ◽  
Protein Phosphatase ◽  
Acyl Carrier Protein ◽  
Protein Biosynthesis ◽  
Acyl Chain ◽  
Biosynthetic Gene Cluster ◽  
Carrier Protein ◽  
Biosynthetic Gene ◽  
Degenerate Primers ◽  
Polyketide Chain

ABSTRACT Tautomycin (TTM), a potent protein phosphatase inhibitor, consists of a polyketide chain containing a spiroketal moiety and an acyl chain bearing a dialkylmaleic anhydride structure. PCR using degenerate primers was used to clone genes from Streptomyces spiroverticillatus for formation of the methoxymalonyl-acyl carrier protein. This locus was found to contain five genes (ttmC, ttmA, ttmD, ttmB, and ttmE), one of which was used as a probe to clone the 110-kb TTM biosynthetic gene cluster. The involvement of the ttmA gene in TTM biosynthesis was confirmed by gene inactivation and mutation complementation experiments.

Cloning, sequencing and heterologous expression of the medermycin biosynthetic gene cluster of Streptomyces sp. AM-7161: towards comparative analysis of the benzoisochromanequinone gene clusters

Microbiology ◽  
2003 ◽  
Vol 149 (7) ◽  
pp. 1633-1645 ◽  
Author(s):  
Koji Ichinose ◽  
Makoto Ozawa ◽  
Keiko Itou ◽  
Kanako Kunieda ◽  
Yutaka Ebizuka
Keyword(s):  
Heterologous Expression ◽  
Gene Cluster ◽  
Polyketide Synthase ◽  
Acyl Carrier Protein ◽  
Streptomyces Coelicolor ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Carrier Protein ◽  
Biosynthetic Gene ◽  
Six Genes

Medermycin is a Streptomyces aromatic C-glycoside antibiotic classified in the benzoisochromanequinones (BIQs), which presents several interesting biosynthetic problems concerning polyketide synthase (PKS), post-PKS tailoring and deoxysugar pathways. The biosynthetic gene cluster for medermycin (the med cluster) was cloned from Streptomyces sp. AM-7161. Completeness of the clone was proved by the heterologous expression of a cosmid carrying the entire med cluster in Streptomyces coelicolor CH999 to produce medermycin. The DNA sequence of the cosmid (36 202 bp) revealed 34 complete ORFs, with an incomplete ORF at either end. Functional assignment of the deduced products was made for PKS and biosynthetically related enzymes, tailoring steps including strereochemical control, oxidation, angolosamine pathway, C-glycosylation, and regulation. The med cluster was estimated to be about 30 kb long, covering 29 ORFs. An unusual characteristic of the cluster is the disconnected organization of the minimal PKS genes: med-ORF23 encoding the acyl carrier protein is 20 kb apart from med-ORF1 and med-ORF2 for the two ketosynthase components. Secondly, the six genes (med-ORF14, 15, 16, 17, 18 and 20) for the biosynthesis of the deoxysugar, angolosamine, are all contiguous. Finally, the finding of a glycosyltransferase gene, med-ORF8, suggests a possible involvement of conventional C-glycosylation in medermycin biosynthesis. Comparison among the three complete BIQ gene clusters – med and those for actinorhodin (act) and granaticin (gra) – revealed some common genes whose deduced functions are unavailable from database searches (the ‘unknowns’). An example is med-ORF5, a homologue of actVI-ORF3 and gra-ORF18, which was highlighted by a recent proteomic analysis of S. coelicolor A3(2).

Albumycin, a new isoindolequinone from Streptomyces albus J1074 harboring the fluostatin biosynthetic gene cluster

2019 ◽  
Vol 72 (5) ◽  
pp. 311-315 ◽  
Author(s):  
Chunshuai Huang ◽  
Chunfang Yang ◽  
Wenjun Zhang ◽  
Yiguang Zhu ◽  
Liang Ma ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Biosynthetic Gene Cluster ◽  
Biosynthetic Gene ◽  
Streptomyces Albus ◽  
Streptomyces Albus J1074

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 Cyclofaulknamycin with the Rare Amino Acid D-capreomycidine Isolated from a Well-Characterized Streptomyces albus Strain

2021 ◽  
Vol 9 (8) ◽  
pp. 1609
Author(s):  
Liliya Horbal ◽  
Marc Stierhof ◽  
Anja Palusczak ◽  
Nikolas Eckert ◽  
Josef Zapp ◽  
...  
Keyword(s):  
Amino Acid ◽  
Gene Cluster ◽  
Pyridoxal Phosphate ◽  
Cyclic Peptide ◽  
Genome Mining ◽  
Biosynthetic Gene Cluster ◽  
Biosynthetic Gene ◽  
Streptomyces Albus ◽  
Cluster Biosynthesis ◽  
First Time

Targeted genome mining is an efficient method of biosynthetic gene cluster prioritization within constantly growing genome databases. Using two capreomycidine biosynthesis genes, alpha-ketoglutarate-dependent arginine beta-hydroxylase and pyridoxal-phosphate-dependent aminotransferase, we identified two types of clusters: one type containing both genes involved in the biosynthesis of the abovementioned moiety, and other clusters including only arginine hydroxylase. Detailed analysis of one of the clusters, the flk cluster from Streptomyces albus, led to the identification of a cyclic peptide that contains a rare D-capreomycidine moiety for the first time. The absence of the pyridoxal-phosphate-dependent aminotransferase gene in the flk cluster is compensated by the XNR_1347 gene in the S. albus genome, whose product is responsible for biosynthesis of the abovementioned nonproteinogenic amino acid. Herein, we report the structure of cyclofaulknamycin and the characteristics of its biosynthetic gene cluster, biosynthesis and bioactivity profile.

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