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Identification and characterization of the spiruchostatin biosynthetic gene cluster enable yield improvement by overexpressing a transcriptional activator.
- Source :
-
Journal of industrial microbiology & biotechnology [J Ind Microbiol Biotechnol] 2014 Sep; Vol. 41 (9), pp. 1457-65. Date of Electronic Publication: 2014 Jun 29. - Publication Year :
- 2014
-
Abstract
- Spiruchostatins A and B are members of the FK228-family of natural products with potent histone deacetylase inhibitory activities and antineoplastic activities. However, their production in the wild-type strain of Pseudomonas sp. Q71576 is low. To improve the yield, the spiruchostatin biosynthetic gene cluster (spi) was first identified by rapid genome sequencing and characterized by genetic mutations. This spi gene cluster encodes a hybrid biosynthetic pathway similar to that encoded by the FK228 biosynthetic gene cluster (dep) in Chromobacterium violaceum No. 968. Each gene cluster contains a pathway regulatory gene (spiR vs. depR), but these two genes encode transcriptional activators of different classes. Overexpression of native spiR or heterologous depR in the wild-type strain of Pseudomonas sp. Q71576 resulted in 268 or 1,285 % increase of the combined titer of spiruchostatins A and B, respectively. RT-PCR analysis indicates that overexpression of heterologous depR upregulates the expression of native spiR.
- Subjects :
- Bacterial Proteins metabolism
Chromobacterium genetics
Gene Expression Regulation, Bacterial
Molecular Sequence Data
Multigene Family
Trans-Activators metabolism
Bacterial Proteins genetics
Biosynthetic Pathways
Chromobacterium metabolism
Depsipeptides biosynthesis
Peptides, Cyclic biosynthesis
Pseudomonas genetics
Trans-Activators genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1476-5535
- Volume :
- 41
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of industrial microbiology & biotechnology
- Publication Type :
- Academic Journal
- Accession number :
- 24973954
- Full Text :
- https://doi.org/10.1007/s10295-014-1474-8