Biosynthesis Based on One-Carbon Mixotrophy.

Area of Science:

• Biotechnology
• Metabolic Engineering
• Industrial Microbiology

Background:

• Biosynthesis using one-carbon (C1) compounds like CO2 and syngas shows industrial promise but faces bottlenecks.
• Limitations include mass-transfer issues, and restricted energy (ATP) and reducing equivalent supply, hindering cell growth and product rates.
• C1-mixotrophy offers an alternative by co-utilizing C1 and organic substrates, complementing autotrophic and heterotrophic pathways.

Purpose of the Study:

• To present and discuss examples of C1-mixotrophy for efficient bulk and fine chemical synthesis.
• To highlight the potential and advantages of C1-mixotrophy as a bioprocess strategy.
• To identify areas for further research and development in C1-based biosynthesis.

Main Methods:

• Acetogenic mixotrophy: Utilizes the reductive acetyl-CoA pathway in native acetogens, enhanced by organic substrates for energy and reducing equivalents.
• Methylotrophic mixotrophy: Employs methanol as a C1 source in native or synthetic methylotrophs, providing carbon and reducing power.
• Heterotrophic mixotrophy: Leverages anaplerotic reactions in heterotrophs, re-wiring metabolism for forced C1 fixation.

Main Results:

• C1-mixotrophy enables efficient synthesis of bulk and fine chemicals by overcoming limitations of pure C1 utilization.
• Acetogenic and methylotrophic approaches enhance C1 fixation and product formation rates.
• Metabolic re-wiring in heterotrophs overcomes yield limitations for C1-based products.

Conclusions:

• C1-mixotrophy using native or synthetic C1 fixation modules is a promising bioprocess strategy for the short to medium term.
• Further quantitative studies on intracellular interactions between C1 fixation and catabolic modules are needed.
• Investigating and overcoming catabolite repression and regulatory mechanisms is crucial for industrial relevance.