Improved production of erythromycin A by expression of a heterologous gene encoding S-adenosylmethionine synthetase.
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.
Wang
Yong
Y
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China. siliangz@163.net
Wang
YiGuang
Y
Chu
Ju
J
Zhuang
Yingping
Y
Zhang
Lixin
L
Zhang
Siliang
S
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D004917:Erythromycin / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism*; D015870:Gene Expression; D005818:Genetic Engineering; D016680:Genome, Bacterial; D008716:Methionine Adenosyltransferase / Q000235:genetics / Q000378:metabolism*; D012436:S-Adenosylmethionine / Q000378:metabolism; D016930:Saccharopolyspora / Q000235:genetics / Q000378:metabolism*; D013171:Spores, Bacterial / Q000254:growth & development; D013302:Streptomyces / Q000201:enzymology*
D001426:Bacterial Proteins; D004917:Erythromycin; D012436:S-Adenosylmethionine; D008716:Methionine Adenosyltransferase