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One-carbon (C1) substrates are attractive feedstocks for biological upgrading as part of a circular, carbon-negative bioeconomy. Nature has evolved a diverse set of C1-trophs that use a variety of pathways. Additionally, intensive effort has recently been invested in developing synthetic C1 assimilation pathways. This complicated landscape presents the question: “What pathways should be used to produce what products from what C1 substrates?” To guide the selection, we calculate and compare maximal theoretical yields for a range of bioproducts from different C1 feedstocks and pathways. The results highlight emerging opportunities to apply metabolic engineering to specific C1 pathways to improve pathway performance. Since the C1 landscape is dynamic, with new discoveries in the biochemistry of native pathways and new synthetic alternatives rapidly emerging, we present detailed procedures for these yield calculations to enable others to easily adapt them to additional scenarios as a foundation for establishing industrially relevant production strains.
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Reverse β-oxidation pathways for efficient chemical production
Abstract Microbial production of fuels, chemicals, and materials has the potential to reduce greenhouse gas emissions and contribute to a sustainable bioeconomy. While synthetic biology allows readjusting of native metabolic pathways for the synthesis of desired products, often these native pathways do not support maximum efficiency and are affected by complex regulatory mechanisms. A synthetic or engineered pathway that allows modular synthesis of versatile bioproducts with minimal enzyme requirement and regulation while achieving high carbon and energy efficiency could be an alternative solution to address these issues. The reverse β-oxidation (rBOX) pathways enable iterative non-decarboxylative elongation of carbon molecules of varying chain lengths and functional groups with only four core enzymes and no ATP requirement. Here, we describe recent developments in rBOX pathway engineering to produce alcohols and carboxylic acids with diverse functional groups, along with other commercially important molecules such as polyketides. We discuss the application of rBOX beyond the pathway itself by its interfacing with various carbon-utilization pathways and deployment in different organisms, which allows feedstock diversification from sugars to glycerol, carbon dioxide, methane, and other substrates.
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- Award ID(s):
- 1916854
- PAR ID:
- 10416127
- Date Published:
- Journal Name:
- Journal of Industrial Microbiology and Biotechnology
- Volume:
- 49
- Issue:
- 2
- ISSN:
- 1367-5435
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1093/jimb/kuac003
