scholarly journals Cofactor Engineering Redirects Secondary Metabolism and Enhances Erythromycin Production in Saccharopolyspora erythraea

2020 ◽  
Vol 9 (3) ◽  
pp. 655-670 ◽  
Author(s):  
Xiaobo Li ◽  
Jun Chen ◽  
Joakim M. Andersen ◽  
Ju Chu ◽  
Peter R. Jensen
Keyword(s):  
Secondary Metabolism ◽  
Saccharopolyspora Erythraea ◽  
Cofactor Engineering ◽  
Erythromycin Production

scholarly journals Uncovering and Engineering a Mini-Regulatory Network of the TetR-Family Regulator SACE_0303 for Yield Improvement of Erythromycin in Saccharopolyspora erythraea

2021 ◽  
Vol 9 ◽  
Author(s):  
Ying Liu ◽  
Sabir Khan ◽  
Panpan Wu ◽  
Bowen Li ◽  
Lanlan Liu ◽  
...  
Keyword(s):  
Regulatory Network ◽  
Target Genes ◽  
Antibacterial Activities ◽  
Saccharopolyspora Erythraea ◽  
High Yield ◽  
Yield Strain ◽  
Yield Improvement ◽  
Erythromycin Production

Erythromycins produced by Saccharopolyspora erythraea have broad-spectrum antibacterial activities. Recently, several TetR-family transcriptional regulators (TFRs) were identified to control erythromycin production by multiplex control modes; however, their regulatory network remains poorly understood. In this study, we report a novel TFR, SACE_0303, positively correlated with erythromycin production in Sac. erythraea. It directly represses its adjacent gene SACE_0304 encoding a MarR-family regulator and indirectly stimulates the erythromycin biosynthetic gene eryAI and resistance gene ermE. SACE_0304 negatively regulates erythromycin biosynthesis by directly inhibiting SACE_0303 as well as eryAI and indirectly repressing ermE. Then, the SACE_0303 binding site within the SACE_0303-SACE_0304 intergenic region was defined. Through genome scanning combined with in vivo and in vitro experiments, three additional SACE_0303 target genes (SACE_2467 encoding cation-transporting ATPase, SACE_3156 encoding a large transcriptional regulator, SACE_5222 encoding α-ketoglutarate permease) were identified and proved to negatively affect erythromycin production. Finally, by coupling CRISPRi-based repression of those three targets with SACE_0304 deletion and SACE_0303 overexpression, we performed stepwise engineering of the SACE_0303-mediated mini-regulatory network in a high-yield strain, resulting in enhanced erythromycin production by 67%. In conclusion, the present study uncovered the regulatory network of a novel TFR for control of erythromycin production and provides a multiplex tactic to facilitate the engineering of industrial actinomycetes for yield improvement of antibiotics.

scholarly journals Engineering of the methylmalonyl-CoA metabolite node of Saccharopolyspora erythraea for increased erythromycin production

2007 ◽  
Vol 9 (3) ◽  
pp. 293-303 ◽  
Author(s):  
A REEVES ◽  
I BRIKUN ◽  
W CERNOTA ◽  
B LEACH ◽  
M GONZALEZ ◽  
...  
Keyword(s):  
Saccharopolyspora Erythraea ◽  
Erythromycin Production

scholarly journals Phenotypes and gene expression profiles of Saccharopolyspora erythraea rifampicin-resistant (rif) mutants affected in erythromycin production

2009 ◽  
Vol 8 (1) ◽  
pp. 18 ◽  
Author(s):  
Elisabetta Carata ◽  
Clelia Peano ◽  
Salvatore M Tredici ◽  
Francesco Ferrari ◽  
Adelfia Talà ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Saccharopolyspora Erythraea ◽  
Erythromycin Production

Reconstruction of the Saccharopolyspora erythraea genome-scale model and its use for enhancing erythromycin production

2012 ◽  
Vol 102 (3) ◽  
pp. 493-502 ◽  
Author(s):  
Cuauhtemoc Licona-Cassani ◽  
Esteban Marcellin ◽  
Lake-Ee Quek ◽  
Shana Jacob ◽  
Lars K. Nielsen
Keyword(s):  
Saccharopolyspora Erythraea ◽  
Scale Model ◽  
Genome Scale ◽  
Genome Scale Model ◽  
Erythromycin Production
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