Partitioning metabolism between growth and product synthesis for coordinated production of wax esters in Acinetobacter baylyi ADP1
Microbial storage compounds, such as wax esters (WE), are potential high-value lipids for the production of specialty chemicals and medicines. Their synthesis, however, is strictly regulated and competes with cell growth, which leads to trade-offs between biomass and product formation. Here, we use...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022
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| Online Access: | https://hdl.handle.net/1721.1/140409 |
| _version_ | 1826193814986948608 |
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| author | Santala, Suvi Santala, Ville Liu, Nian Stephanopoulos, Gregory |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering Santala, Suvi Santala, Ville Liu, Nian Stephanopoulos, Gregory |
| author_sort | Santala, Suvi |
| collection | MIT |
| description | Microbial storage compounds, such as wax esters (WE), are potential high-value lipids for the production of specialty chemicals and medicines. Their synthesis, however, is strictly regulated and competes with cell growth, which leads to trade-offs between biomass and product formation. Here, we use metabolic engineering and synergistic substrate cofeeding to partition the metabolism of Acinetobacter baylyi ADP1 into two distinct modules, each dedicated to cell growth and WE biosynthesis, respectively. We first blocked the glyoxylate shunt and upregulated the WE synthesis pathway to direct the acetate substrate exclusively for WE synthesis, then we controlled the supply of gluconate so it could be used exclusively for cell growth and maintenance. We show that the two modules are functionally independent from each other, allowing efficient lipid accumulation while maintaining active cell growth. Our strategy resulted in 7.2- and 4.2-fold improvements in WE content and productivity, respectively, and the product titer was enhanced by 8.3-fold over the wild type strain. Notably, during a 24-h cultivation, a yield of 18% C-WE/C-total-substrates was achieved, being the highest reported for WE biosynthesis. This study provides a simple, yet powerful, means of controlling cellular operations and overcoming some of the fundamental challenges in microbial storage lipid production. |
| first_indexed | 2024-09-23T09:45:32Z |
| format | Article |
| id | mit-1721.1/140409 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T09:45:32Z |
| publishDate | 2022 |
| publisher | Wiley |
| record_format | dspace |
| spelling | mit-1721.1/1404092024-06-06T19:30:21Z Partitioning metabolism between growth and product synthesis for coordinated production of wax esters in Acinetobacter baylyi ADP1 Santala, Suvi Santala, Ville Liu, Nian Stephanopoulos, Gregory Massachusetts Institute of Technology. Department of Chemical Engineering Microbial storage compounds, such as wax esters (WE), are potential high-value lipids for the production of specialty chemicals and medicines. Their synthesis, however, is strictly regulated and competes with cell growth, which leads to trade-offs between biomass and product formation. Here, we use metabolic engineering and synergistic substrate cofeeding to partition the metabolism of Acinetobacter baylyi ADP1 into two distinct modules, each dedicated to cell growth and WE biosynthesis, respectively. We first blocked the glyoxylate shunt and upregulated the WE synthesis pathway to direct the acetate substrate exclusively for WE synthesis, then we controlled the supply of gluconate so it could be used exclusively for cell growth and maintenance. We show that the two modules are functionally independent from each other, allowing efficient lipid accumulation while maintaining active cell growth. Our strategy resulted in 7.2- and 4.2-fold improvements in WE content and productivity, respectively, and the product titer was enhanced by 8.3-fold over the wild type strain. Notably, during a 24-h cultivation, a yield of 18% C-WE/C-total-substrates was achieved, being the highest reported for WE biosynthesis. This study provides a simple, yet powerful, means of controlling cellular operations and overcoming some of the fundamental challenges in microbial storage lipid production. 2022-02-16T16:11:19Z 2022-02-16T16:11:19Z 2021-03-15 Article http://purl.org/eprint/type/JournalArticle 0006-3592 1097-0290 https://hdl.handle.net/1721.1/140409 Santala, S., Santala, V., Liu, N., & Stephanopoulos, G. (2021). Partitioning metabolism between growth and product synthesis for coordinated production of wax esters in Acinetobacter baylyi ADP1. Biotechnology and Bioengineering. 118, 2283– 2292. en http://dx.doi.org/10.1002/bit.27740 Biotechnology and Bioengineering Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Wiley Wiley |
| spellingShingle | Santala, Suvi Santala, Ville Liu, Nian Stephanopoulos, Gregory Partitioning metabolism between growth and product synthesis for coordinated production of wax esters in Acinetobacter baylyi ADP1 |
| title | Partitioning metabolism between growth and product synthesis for coordinated production of wax esters in Acinetobacter baylyi ADP1 |
| title_full | Partitioning metabolism between growth and product synthesis for coordinated production of wax esters in Acinetobacter baylyi ADP1 |
| title_fullStr | Partitioning metabolism between growth and product synthesis for coordinated production of wax esters in Acinetobacter baylyi ADP1 |
| title_full_unstemmed | Partitioning metabolism between growth and product synthesis for coordinated production of wax esters in Acinetobacter baylyi ADP1 |
| title_short | Partitioning metabolism between growth and product synthesis for coordinated production of wax esters in Acinetobacter baylyi ADP1 |
| title_sort | partitioning metabolism between growth and product synthesis for coordinated production of wax esters in acinetobacter baylyi adp1 |
| url | https://hdl.handle.net/1721.1/140409 |
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