1. Identification and characterization of the spiruchostatin biosynthetic gene cluster enable yield improvement by overexpressing a transcriptional activator.
- Author
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Potharla, Vishwakanth, Wang, Cheng, and Cheng, Yi-Qiang
- Subjects
GENETIC transcription ,PEPTIDES ,BIOSYNTHESIS ,GENE expression ,NATURAL products ,HISTONE deacetylase inhibitors ,ANTINEOPLASTIC agents - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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