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

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.

2010 ◽  
Vol 77 (4) ◽  
pp. 1508-1511 ◽  
Author(s):  
Vishwakanth Y. Potharla ◽  
Shane R. Wesener ◽  
Yi-Qiang Cheng

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.


2019 ◽  
Vol 17 (3) ◽  
pp. 461-466 ◽  
Author(s):  
Taro Shiraishi ◽  
Makoto Nishiyama ◽  
Tomohisa Kuzuyama

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


2006 ◽  
Vol 188 (11) ◽  
pp. 4142-4147 ◽  
Author(s):  
Chunhua Zhao ◽  
Jianhua Ju ◽  
Steven D. Christenson ◽  
Wyatt C. Smith ◽  
Danfeng Song ◽  
...  

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.


2019 ◽  
Vol 72 (5) ◽  
pp. 311-315 ◽  
Author(s):  
Chunshuai Huang ◽  
Chunfang Yang ◽  
Wenjun Zhang ◽  
Yiguang Zhu ◽  
Liang Ma ◽  
...  

1998 ◽  
Vol 5 (11) ◽  
pp. 647-659 ◽  
Author(s):  
Koji Ichinose ◽  
David J. Bedford ◽  
Diethild Tornus ◽  
Andreas Bechthold ◽  
Maureen J. Bibb ◽  
...  

2005 ◽  
Vol 49 (1) ◽  
pp. 230-240 ◽  
Author(s):  
Joshua A. V. Blodgett ◽  
Jun Kai Zhang ◽  
William W. Metcalf

ABSTRACT A fosmid library from genomic DNA of Streptomyces viridochromogenes DSM 40736 was constructed and screened for the presence of genes known to be involved in the biosynthesis of phosphinothricin tripeptide (PTT). Eight positives were identified, one of which was able to confer PTT biosynthetic capability upon Streptomyces lividans after integration of the fosmid into the chromosome of this heterologous host. Sequence analysis of the 40,241-bp fosmid insert revealed 29 complete open reading frames (ORFs). Deletion analysis demonstrated that a minimum set of 24 ORFs were required for PTT production in the heterologous host. Sequence analysis revealed that most of these PTT genes have been previously identified in either S. viridochromogenes or S. hygroscopicus (or both), although only 11 out of 24 of these ORFs have experimentally defined functions. Three previously unknown genes within the cluster were identified and are likely to have roles in the stepwise production of phosphonoformate from phosphonoacetaldehyde. This is the first report detailing the entire PTT gene cluster from any producing streptomycete.


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