ArticleApplied and environmental microbiology2008
Genetic modulation of the overexpression of tailoring genes eryK and eryG leading to the improvement of erythromycin A purity and production in Saccharopolyspora erythraea fermentation.
Article in Applied and environmental microbiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 83 citations in OpenAlex.
- Coupled strategy based on regulator manipulation and medium optimization empowers the biosynthetic overproduction of lincomycin.Synthetic and systems biotechnology · 2024Article
- Improving spinosad production by tuning expressions of the forosamine methyltransferase and the forosaminyl transferase to reduce undesired less active byproducts in the heterologous host Streptomyces albus J1074.Microbial cell factories · 2023Article
- PhoP- and GlnR-mediated regulation of metK transcription and its impact upon S-adenosyl-methionine biosynthesis in Saccharopolyspora erythraea.Microbial cell factories · 2022Article
- Acyltransferase AniI, a Tailoring Enzyme with Broad Substrate Tolerance for High-Level Production of Anisomycin.Applied and environmental microbiology · 2021Article
- Optimization of tetramycin production in Streptomyces ahygroscopicus S91.Journal of biological engineering · 2021Article
- Recent Advances in the Synthetic Biology of Natural Drugs.Frontiers in bioengineering and biotechnology · 2021Review
- The Expression of NOX From Synthetic Promoters Reveals an Important Role of the Redox Status in Regulating Secondary Metabolism ofFrontiers in bioengineering and biotechnology · 2020Article
- Co-expression of a SARP Family Activator ChlF2 and a Type II Thioesterase ChlK Led to High Production of Chlorothricin inFrontiers in bioengineering and biotechnology · 2020Article
- Characterization and engineering of the Lrp/AsnC family regulator SACE_5717 for erythromycin overproduction in Saccharopolyspora erythraea.Journal of industrial microbiology & biotechnology · 2019Article
- Modulation of kanamycin B and kanamycin A biosynthesis in Streptomyces kanamyceticus via metabolic engineering.PloS one · 2017Article
- Inactivation of SACE_3446, a TetR family transcriptional regulator, stimulates erythromycin production inSynthetic and systems biotechnology · 2016Article
- Dissecting and engineering of the TetR family regulator SACE_7301 for enhanced erythromycin production in Saccharopolyspora erythraea.Microbial cell factories · 2014Article
- SACE_3986, a TetR family transcriptional regulator, negatively controls erythromycin biosynthesis in Saccharopolyspora erythraea.Journal of industrial microbiology & biotechnology · 2014Article
- Article
- SACE_5599, a putative regulatory protein, is involved in morphological differentiation and erythromycin production in Saccharopolyspora erythraea.Microbial cell factories · 2013Article
- Systems perspectives on erythromycin biosynthesis by comparative genomic and transcriptomic analyses of S. erythraea E3 and NRRL23338 strains.BMC genomics · 2013Article
- The logic, experimental steps, and potential of heterologous natural product biosynthesis featuring the complex antibiotic erythromycin A produced through E. coli.Journal of visualized experiments : JoVE · 2013Article
- An erythromycin process improvement using the diethyl methylmalonate-responsive (Dmr) phenotype of the Saccharopolyspora erythraea mutB strain.Applied microbiology and biotechnology · 2012Article
- Simultaneous production and partitioning of heterologous polyketide and isoprenoid natural products in an Escherichia coli two-phase bioprocess.Journal of industrial microbiology & biotechnology · 2011Article
- Toward improvement of erythromycin A production in an industrial Saccharopolyspora erythraea strain via facilitation of genetic manipulation with an artificial attB site for specific recombination.Applied and environmental microbiology · 2011Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Erythromycin A (Er-A) is the most potent and clinically important member in the Er family produced by Saccharopolyspora erythraea. Er-B and Er-C, which are biologically much less active and cause greater side effects than Er-A, serve as the intermediates for Er-A biosynthesis and impurities in fermentation processes of many industrial strains. In this study, systematical modulation of the amounts of tailoring enzymes EryK (a P450 hydroxylase) and EryG (an S-adenosylmethionine-dependent O-methyltransferase) was carried out by genetic engineering in S. erythraea, including alterations of gene copy number ratio and organization and integrating the locus on the chromosome by homologous recombination. Introduction of additional eryK and eryG genes into S. erythraea showed significant impacts on their transcription levels and enhanced the biotransformation process from Er-D to Er-A with gene dose effects. At the eryK/eryG copy number ratio of 3:2 as well as their resultant transcript ratio of around 2.5:1 to 3.0:1, Er-B and Er-C were nearly completely eliminated and accordingly converted to Er-A, and the Er titer was improved by around 25% in the recombinant strain ZL1004 (genotype PermK*-K-K-G + PermE*-K + PermA*-G) and ZL1007 (genotype PermK*-K-G-K + PermE*-K + PermA*-G). This study may contribute to the continuous efforts toward further evaluation of the Er-producing system, with the aims of improving Er-A purity and production at the fermentation stage and lowering the production costs and environmental concerns in industry.
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