Identification and characterization of the spiruchostatin biosynthetic gene cluster enable yield improvement by overexpressing a transcriptional activator. (1st September 2014)

• Record Type: Journal Article
• Authors: Potharla, Vishwakanth Y; Wang, Cheng; Cheng, Yi-Qiang
• Is Part Of: Journal of industrial microbiology & biotechnology. Volume 41:Number 9(2014)
• Page Start: 1457
• Page End: 1465
• Publication Date: 2014-09-01
• Subjects: Spiruchostatins -- Pseudomonas sp. Q71576 -- Biosynthesis -- Genetic engineering -- Yield improvement; Industrial microbiology -- Periodicals; 660.62
• DOI: 10.1007/s10295-014-1474-8
• Languages: English
• ISSNs: 1367-5435

Abstract

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 .