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Improved production of erythromycin A by expression of a heterologous gene encoding S-adenosylmethionine synthetase
Authors:Yong Wang  YiGuang Wang  Ju Chu  Yingping Zhuang  Lixin Zhang  Siliang Zhang
Institution:(1) State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China;(2) Institute of Medical Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Tiantan, Beijing, 100050, China;(3) Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, 100080, China;(4) South China Sea Institute of Oceanology, Chinese Academy of Sciences (CAS), Beijing, 510301, China;(5) Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences (CAS), Guangzhou, 510663, China;(6) SynerZ Pharmaceuticals, Lexington, MA 02421, USA
Abstract:An S-adenosylmethionine synthetase (SAM-s) gene from Streptomyces spectabilis was integrated along with vector DNA into the chromosome of a Saccharopolyspora erythraea E2. Elevated production of SAM was observed in the recombinant strain Saccharopolyspora erythraea E1. The results from the bioassay showed that the titer of erythromycin was increased from 920 IU ml−1 by E2 to approximately 2,000 IU ml−1 by E1. High performance liquid chromatography (HPLC) analysis revealed that there was a 132% increase in erythromycin A compared with the original strain, while the erythromycin B, the main impurity component in erythromycin, was decreased by 30%. The sporulation process was inhibited, while the SAM-s gene was expressed. The addition of the exogenous SAM also inhibited sporulation and promoted an increase in erythromycin titers. An erratum to this article can be found at
Keywords:S-adenosylmethionine synthetase  Erythromycin A  Precision engineering            Saccharopolyspora erythraea
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