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Improved production of secreted heterologous enzyme in Bacillus subtilis strain MGB874 via modification of glutamate metabolism and growth conditions

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논문

Improved production of secreted heterologous enzyme in Bacillus subtilis strain MGB874 via modification of glutamate metabolism and growth conditions

학술지

Microbial cell factories

저자명

Manabe, Kenji; Kageyama, Yasushi; Morimoto, Takuya; Shimizu, Eri; Takahashi, Hiroki; Kanaya, Shigehiko; Ara, Katsutoshi; Ozaki, Katsuya; Ogasawara, Naotake

초록

<P><B>Background</B></P><P>The <I>Bacillus subtilis</I> genome-reduced strain MGB874 exhibits enhanced production of exogenous extracellular enzymes under batch fermentation conditions. We predicted that deletion of the gene for RocG, a bi-functional protein that acts as a glutamate dehydrogenase and an indirect repressor of glutamate synthesis, would improve glutamate metabolism, leading to further increased enzyme production. However, deletion of <I>rocG</I> dramatically decreased production of the alkaline cellulase Egl-237 in strain MGB874 (strain 874&#x2206;rocG).</P><P><B>Results</B></P><P>Transcriptome analysis and cultivation profiles suggest that this phenomenon is attributable to impaired secretion of alkaline cellulase Egl-237 and nitrogen starvation, caused by decreased external pH and ammonium depletion, respectively. With NH<SUB>3</SUB>-pH auxostat fermentation, production of alkaline cellulase Egl-237 in strain 874&#x2206;rocG was increased, exceeding that in the wild-type-background strain 168&#x2206;rocG. Notably, in strain 874&#x2206;rocG, high enzyme productivity was observed throughout cultivation, possibly due to enhancement of metabolic flux from 2-oxoglutarate to glutamate and generation of metabolic energy through activation of the tricarboxylic acid (TCA) cycle. The level of alkaline cellulase Egl-237 obtained corresponded to about 5.5 g l<SUP>-1</SUP>, the highest level reported so far.</P><P><B>Conclusions</B></P><P>We found the highest levels of production of alkaline cellulase Egl-237 with the reduced-genome strain 874&#x2206;rocG and using the NH<SUB>3</SUB>-pH auxostat. Deletion of the glutamate dehydrogenase gene <I>rocG</I> enhanced enzyme production via a prolonged auxostat fermentation, possibly due to improved glutamate synthesis and enhanced generation of metabolism energy.</P>

발행연도

2013

발행기관

BioMed Central

ISSN

1475-2859

12

페이지

pp.18-18

주제어

Bacillus subtilis; Protein secretion; Genome reduction; Glutamate metabolism

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논문; 2013-12-31

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