Linked Life Data

20534557

Source:http://linkedlifedata.com/resource/pubmed/id/20534557

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
25
pubmed:dateCreated
2010-6-23
pubmed:abstractText
Avermectin and its analogues are produced by the actinomycete Streptomyces avermitilis and are widely used in the field of animal health, agriculture, and human health. Here we have adopted a practical approach to successfully improve avermectin production in an industrial overproducer. Transcriptional levels of the wild-type strain and industrial overproducer in production cultures were monitored using microarray analysis. The avermectin biosynthetic genes, especially the pathway-specific regulatory gene, aveR, were up-regulated in the high-producing strain. The upstream promoter region of aveR was predicted and proved to be directly recognized by sigma(hrdB) in vitro. A mutant library of hrdB gene was constructed by error-prone PCR and selected by high-throughput screening. As a result of evolved hrdB expressed in the modified avermectin high-producing strain, 6.38 g/L of avermectin B1a was produced with over 50% yield improvement, in which the transcription level of aveR was significantly increased. The relevant residues were identified to center in the conserved regions. Engineering of the hrdB gene can not only elicit the overexpression of aveR but also allows for simultaneous transcription of many other genes. The results indicate that manipulating the key genes revealed by reverse engineering can effectively improve the yield of the target metabolites, providing a route to optimize production in these complex regulatory systems.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1091-6490
pubmed:author
pubmed:issnType
Electronic
pubmed:day
22
pubmed:volume
107
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11250-4
pubmed:dateRevised
2010-12-23
pubmed:meshHeading
pubmed-meshheading:20534557-Bacterial Proteins, pubmed-meshheading:20534557-Base Sequence, pubmed-meshheading:20534557-Bioengineering, pubmed-meshheading:20534557-DNA-Binding Proteins, pubmed-meshheading:20534557-DNA-Directed RNA Polymerases, pubmed-meshheading:20534557-Gene Expression Regulation, Bacterial, pubmed-meshheading:20534557-Gene Library, pubmed-meshheading:20534557-Genetic Engineering, pubmed-meshheading:20534557-Ivermectin, pubmed-meshheading:20534557-Molecular Sequence Data, pubmed-meshheading:20534557-Mutation, pubmed-meshheading:20534557-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:20534557-Promoter Regions, Genetic, pubmed-meshheading:20534557-Sequence Homology, Nucleic Acid, pubmed-meshheading:20534557-Sigma Factor, pubmed-meshheading:20534557-Streptomyces, pubmed-meshheading:20534557-Transcription, Genetic
pubmed:year
2010
pubmed:articleTitle
Reverse biological engineering of hrdB to enhance the production of avermectins in an industrial strain of Streptomyces avermitilis.
pubmed:affiliation
Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100190, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't