Presentation Information
[P01-062]Development of a programmable therapeutic bacterium, Escherichia coli Nissle 1917, for (S)-Equol production using a novel synthetic biosensor
Sung Won Cho1, ○Junsu Jang1, Jina Yang6, Sang Woo Seo1,2,3,4,5 (1. School of Chemical and Biological engineering, Seoul National University (Korea), 2. Interdisciplinary Program in Bioengineering, Seoul National University (Korea), 3. Institute of Chemical Processes (Korea), 4. Bio-MAX Institute (Korea), 5. Institute of Bio Engineering, Seoul National University (Korea), 6. School of Chemical and Biological engineering, Jeju National University (Korea))
Keywords:
Biosensor,Synthetic biology,Therapeutic bacterium,Isoflavone
Equol, a metabolite of soy isoflavone daidzein, has been shown to possess several health benefits, such as alleviating menopausal symptoms, preventing osteoporosis, and reducing the risk of prostate cancer. However, equol production is limited by low conversion rates in gut microbiota and is only available with a subset of individuals with specific gut bacteria. Therefore, developing engineered probiotics that efficiently produce equol is desirable.
To achieve this goal, here we developed a novel substrate-inducible promoter system to enhance equol production while minimizing metabolic burden and reducing the need for expensive inducers. This inducible system was constructed by fusing the polymerase binding region in the promoter of lacI gene from Escherichia coli and the operator region in the promoter of the isoflavone-sensitive operon from Bradyrhizobium japonicum. We further optimized the synthetic promoter by testing various arrangements of the operator
region. Then the synthetic inducible system was applied for the codon-optimized equol production. Furthermore, the synthetically designed pathway was integrated into the genetically optimized Escherichia coli Nissle 1917 as a therapeutic probiotic. The engineered bacteria successfully produced equol under no additional inducer, demonstrating its potential as a desirable live bacterial therapeutic. Our study presents a promising approach to produce high-value added molecules using substrate-inducible promoters in engineered bacteria, which could pave the way for the development of novel probiotics for human health.
To achieve this goal, here we developed a novel substrate-inducible promoter system to enhance equol production while minimizing metabolic burden and reducing the need for expensive inducers. This inducible system was constructed by fusing the polymerase binding region in the promoter of lacI gene from Escherichia coli and the operator region in the promoter of the isoflavone-sensitive operon from Bradyrhizobium japonicum. We further optimized the synthetic promoter by testing various arrangements of the operator
region. Then the synthetic inducible system was applied for the codon-optimized equol production. Furthermore, the synthetically designed pathway was integrated into the genetically optimized Escherichia coli Nissle 1917 as a therapeutic probiotic. The engineered bacteria successfully produced equol under no additional inducer, demonstrating its potential as a desirable live bacterial therapeutic. Our study presents a promising approach to produce high-value added molecules using substrate-inducible promoters in engineered bacteria, which could pave the way for the development of novel probiotics for human health.
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