Inactivation of SACE_3446, a TetR family transcriptional regulator, stimulates erythromycin production in Saccharopolyspora erythraea.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Weaver, David T
MetadataShow full item record
AbstractErythromycin A is a widely used antibiotic produced by Saccharopolyspora erythraea; however, its biosynthetic cluster lacks a regulatory gene, limiting the yield enhancement via regulation engineering of S. erythraea. Herein, six TetR family transcriptional regulators (TFRs) belonging to three genomic context types were individually inactivated in S. erythraea A226, and one of them, SACE_3446, was proved to play a negative role in regulating erythromycin biosynthesis. EMSA and qRT-PCR analysis revealed that SACE_3446 covering intact N-terminal DNA binding domain specifically bound to the promoter regions of erythromycin biosynthetic gene eryAI, the resistant gene ermE and the adjacent gene SACE_3447 (encoding a long-chain fatty-acid CoA ligase), and repressed their transcription. Furthermore, we explored the interaction relationships of SACE_3446 and previously identified TFRs (SACE_3986 and SACE_7301) associated with erythromycin production. Given demonstrated relatively independent regulation mode of SACE_3446 and SACE_3986 in erythromycin biosynthesis, we individually and concomitantly inactivated them in an industrial S. erythraea WB. Compared with WB, the WBΔ3446 and WBΔ3446Δ3986 mutants respectively displayed 36% and 65% yield enhancement of erythromycin A, following significantly elevated transcription of eryAI and ermE. When cultured in a 5 L fermentor, erythromycin A of WBΔ3446 and WBΔ3446Δ3986 successively reached 4095 mg/L and 4670 mg/L with 23% and 41% production improvement relative to WB. The strategy reported here will be useful to improve antibiotics production in other industrial actinomycete.
CitationInactivation of SACE_3446, a TetR family transcriptional regulator, stimulates erythromycin production in Saccharopolyspora erythraea. 2016, 1 (1):39-46 Synth Syst Biotechnol
AffiliationHIPS, Helmholtz-Institut für pharmazeutische Forschung Saarland, Universitätscampus E8.1,66123 Saarbrücken, Germany.
The following license files are associated with this item:
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-sa/4.0/
- Dissecting and engineering of the TetR family regulator SACE_7301 for enhanced erythromycin production in Saccharopolyspora erythraea.
- Authors: Wu H, Chen M, Mao Y, Li W, Liu J, Huang X, Zhou Y, Ye BC, Zhang L, Weaver DT, Zhang B
- Issue date: 2014 Nov 13
- SACE_3986, a TetR family transcriptional regulator, negatively controls erythromycin biosynthesis in Saccharopolyspora erythraea.
- Authors: Wu P, Pan H, Zhang C, Wu H, Yuan L, Huang X, Zhou Y, Ye BC, Weaver DT, Zhang L, Zhang B
- Issue date: 2014 Jul
- Capturing the target genes of BldD in Saccharopolyspora erythraea using improved genomic SELEX method.
- Authors: Wu H, Mao Y, Chen M, Pan H, Huang X, Ren M, Wu H, Li J, Xu Z, Yuan H, Geng M, Weaver DT, Zhang L, Zhang B
- Issue date: 2015 Mar
- Engineering of an Lrp family regulator SACE_Lrp improves erythromycin production in Saccharopolyspora erythraea.
- Authors: Liu J, Chen Y, Wang W, Ren M, Wu P, Wang Y, Li C, Zhang L, Wu H, Weaver DT, Zhang B
- Issue date: 2017 Jan
- SACE_5599, a putative regulatory protein, is involved in morphological differentiation and erythromycin production in Saccharopolyspora erythraea.
- Authors: Kirm B, Magdevska V, Tome M, Horvat M, Karničar K, Petek M, Vidmar R, Baebler S, Jamnik P, Fujs Š, Horvat J, Fonovič M, Turk B, Gruden K, Petković H, Kosec G
- Issue date: 2013 Dec 17