View : 11 Download: 3

Roles of fkbN in positive regulation and tcs7 in negative regulation of FK506 biosynthesis in streptomyces sp. strain KCTC 11604BP

Title
Roles of fkbN in positive regulation and tcs7 in negative regulation of FK506 biosynthesis in streptomyces sp. strain KCTC 11604BP
Authors
Mo S.J.Yoo Y.J.Ban Y.H.Lee S.-K.Kim E.Suh J.-W.Yoon Y.J.
Ewha Authors
윤여준
SCOPUS Author ID
윤여준scopus
Issue Date
2012
Journal Title
Applied and Environmental Microbiology
ISSN
0099-2240JCR Link
Citation
vol. 78, no. 7, pp. 2249 - 2255
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
FK506 is an important 23-member polyketide macrolide with immunosuppressant activity. Its entire biosynthetic gene cluster was previously cloned from Streptomyces sp. strain KCTC 11604BP, and sequence analysis identified three putative regulatory genes, tcs2, tcs7, and fkbN, which encode proteins with high similarity to the AsnC family transcriptional regulators, LysR-type transcriptional regulators, and LAL family transcriptional regulators, respectively. Overexpression and in-frame deletion of tcs2 did not affect the production of FK506 or co-occurring FK520 compared to results for the wild-type strain, suggesting that tcs2 is not involved in their biosynthesis. fkbN overexpression improved the levels of FK506 and FK520 production by approximately 2.0-fold, and a deletion of fkbN caused the complete loss of FK506 and FK520 production. Although the overexpression of tcs7 decreased the levels of FK506 and FK520 production slightly, a deletion of tcs7 caused 1.9-fold and 1.5-fold increases in FK506 and FK520 production, respectively. Finally, fkbN overexpression in the tcs7 deletion strain resulted in a 4.0-fold (21 mg liter-1) increase in FK506 production compared to that by the wild-type strain. This suggests that fkbN encodes a positive regulatory protein essential for FK506/FK520 biosynthesis and that the gene product of tcs7 negatively regulates their biosynthesis, demonstrating the potential of exploiting this information for strain improvement. Semiquantitative reverse transcription-PCR (RTPCR) analyses of the transcription levels of the FK506 biosynthetic genes in the wild-type and mutant strains proved that most of the FK506 biosynthetic genes are regulated by fkbN in a positive manner and negatively by tcs7. © 2012, American Society for Microbiology.
DOI
10.1128/AEM.06766-11
Appears in Collections:
자연과학대학 > 화학·나노과학전공 > Journal papers
Files in This Item:
001.pdf(972.74 kB)Download
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE