Production of the antibiotic FR-008/candicidin in Streptomyces sp. FR-008 is co-regulated by two regulators, FscRI and FscRIV, from different transcription factor families

Zhang, Peipei; Zhao, Zhihui; Li, Hao; Chen, Xiu-Lan; Deng, Zixin; Bai, Linquan; Pang, Xiuhua

doi:10.1099/mic.0.000033

Cited by 30 publications

(35 citation statements)

References 29 publications

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Section: Resultsmentioning

confidence: 99%

“…strain FR-008 and is required for the expression of 16 out of 21 genes within the gene cluster (26). DNA motifs consistent with those recognized by PimM-type regulators were identified upstream of fscA , fscB , and fscD , which each encode a type I PKS, and fscRIV , which is a LAL regulator (a large ATP-binding regulator of the LuxR type) (26). The amino acid sequences of FscRI FR-008 and FscRI S4 are 100% identical, and inspection of the S. albus S4 genome sequence revealed the presence of DNA motifs identical to those upstream of fscA , fscB , fscD , and fscMI in Streptomyces sp.…”

Section: Resultsmentioning

confidence: 99%

“…We initially sought to verify this hypothesis by performing electrophoretic mobility shift assays with purified FscRI protein; however, FscRI harboring either an N-terminal or a C-terminal hexahistidine tag was insoluble when overproduced by Escherichia coli (data not shown), which was surprising given than His 6 -FscRI FR-008 was reportedly soluble (26). Nevertheless, we adopted a ChIP-sequencing approach to determine if the antB and antC promoters were bound by FscRI in vivo .…”

Section: Resultsmentioning

confidence: 99%

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Coordinate Regulation of Antimycin and Candicidin Biosynthesis

McLean

Hoskisson

Seipke

2016

mSphere

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Natural products produced by members of the phylum Actinobacteria underpin many industrially and medically important compounds; however, the majority of the ~30 biosynthetic pathways harbored by an average species are not expressed in the laboratory. Understanding the diversity of regulatory strategies controlling the expression of these pathways is therefore critical if their biosynthetic potential is to be explored for new drug leads. Our findings reveal that the candicidin cluster-situated regulator FscRI coordinately controls the biosynthesis of both candicidin and antimycin, which is the first observation of cross-regulation of disparate biosynthetic gene clusters specifying unrelated natural products. We anticipate that this will emerge as a major strategy by which members of the phylum Actinobacteria coordinately produce natural products, which will advance our understanding of how the expression of secondary metabolism is controlled and will aid the pursuit of “silent” biosynthetic pathway activation.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Coordinate Regulation of Antimycin and Candicidin Biosynthesis

McLean

Hoskisson

Seipke

2016

mSphere

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“…1c, d): NysRIV (67.2 % identity) of the nystatin-producing strain S. noursei ATCC11455 [30], AmphRIV (64.02 % identity) of the amphotericin-producing strain S. nodosus ATCC14899 [7], and FscRI (65.08 % identity) of the FR-008/candicidinproducing strain Streptomyces sp. FR-008 [35]. All these regulators combined an N terminal PAS domain with a C terminal HTH motif of the LuxR type.…”

Section: Resultsmentioning

confidence: 98%

Functional manipulations of the tetramycin positive regulatory gene ttmRIV to enhance the production of tetramycin A and nystatin A1 in Streptomyces ahygroscopicus

Cui

Shao

et al. 2015

Journal of Industrial Microbiology and Biotechnology

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A putative regulatory gene ttmRIV located in the tetramycin biosynthetic gene cluster was found in Streptomyces ahygroscopicus. In-frame deletion of ttmRIV led to abolishment of tetramycin and significant enhancement of nystatin A1, whose production reached 2.1-fold of the H42 parental strain. Gene complementation by an integrative plasmid carrying ttmRIV restored tetramycin biosynthesis revealed that ttmRIV was indispensable to tetramycin biosynthesis. Gene expression analysis of the H42 strain and its mutant strain ΔttmRIV via reverse transcriptase-PCR of the tetramycin gene cluster demonstrated that the expression levels of most biosynthetic genes were reduced in ΔttmRIV. Results of electrophoretic mobility shift assays showed that TtmRIV bound the putative promoters of several genes in the tetramycin pathway. Thus, TtmRIV is a pathway-specific positive regulator activating the transcription of the tetramycin gene cluster in S. ahygroscopicus. Providing an additional copy of ttmRIV under the control of the ermEp* promoter in the H42 strain boosted tetramycin A production to 3.3-fold.

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“…Regulation has been investigated for nystatin, tetramycin, and FR008 biosynthesis (Caffrey et al, 2008;Cui et al, 2015;Zhang et al, 2015), but the most detailed studies have been carried out on pimaricin (Aparicio et al, 2016).…”

Section: Regulation Of Polyene Biosynthesis and Use Of Genome Sequencmentioning

confidence: 99%

Polyene macrolide biosynthesis in streptomycetes and related bacteria: recent advances from genome sequencing and experimental studies

Caffrey

Poire

Sheehan

et al. 2016

Appl Microbiol Biotechnol

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Production of the antibiotic FR-008/candicidin in Streptomyces sp. FR-008 is co-regulated by two regulators, FscRI and FscRIV, from different transcription factor families

Cited by 30 publications

References 29 publications

Coordinate Regulation of Antimycin and Candicidin Biosynthesis

Coordinate Regulation of Antimycin and Candicidin Biosynthesis

Functional manipulations of the tetramycin positive regulatory gene ttmRIV to enhance the production of tetramycin A and nystatin A1 in Streptomyces ahygroscopicus

Polyene macrolide biosynthesis in streptomycetes and related bacteria: recent advances from genome sequencing and experimental studies

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