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Published on: December 15, 2017
Reprogramming Corynebacterium glutamicum metabolism to efficiently synthesis protocatechuic acid from flask to pilot
Hao Shi1, Haowen Zhu1, Tianwei Tan1
1National Energy R&D Center for Biorefinery, Beijing University of Chemical Technology, 100029 Beijing, People's Republic of China; State Key Laboratory of Green Biomanufacturing, Beijing University of Chemical Technology, Beijing 100029, People's Republic of China; Beijing University of Chemical Technology, Beijing 100029, People's Republic of China; Biorefinery Engineering Research Center of the Ministry of Education, Beijing 102209, People's Republic of China.
Metabolic engineering of C. glutamicum significantly boosted protocatechuic acid (PCA) production. This breakthrough enables high-yield, cost-effective production of PCA for potential use as a feed additive.
Area of Science:
- Biotechnology
- Metabolic Engineering
- Synthetic Biology
Background:
- Protocatechuic acid (PCA) is a valuable compound found in Chinese herbal medicine, but its extraction and preservation face challenges.
- Developing efficient production methods for PCA is crucial for its wider application.
Purpose of the Study:
- To design a precise metabolic network model of C. glutamicum for PCA production.
- To engineer C. glutamicum for enhanced PCA yield and activity.
Main Methods:
- Flux Balance Analysis (FBA) was used to guide metabolic engineering strategies.
- Key strategies included enhancing the pentose phosphate pathway (PPP) and shikimic acid pathway, and eliminating PCA degradation.
- Heterologous PCA biosynthesis pathways were implemented in C. glutamicum.
Main Results:
- PCA titer reached 22.11 g/L in shake flasks.
- Transcriptome analysis indicated improved carbon flow and energy metabolism in engineered strains.
- Pilot-scale bioreactors achieved 63.22 g/L (5L) and 52.77 g/L (100L) PCA, representing maximum documented yields.
- Mass-produced PCA demonstrated effective antibacterial and antioxidant activities.
Conclusions:
- Metabolic engineering strategies successfully enhanced PCA production in C. glutamicum.
- The developed methods offer a pathway for efficient, high-value chemical production.
- The mass-produced PCA shows promise as a feed additive for livestock.
