Production of nonnatural straight-chain amino acid 6-aminocaproate via an artificial iterative carbon-chain-extension cycle
Bioplastics produced from microbial source are promising green alternatives to traditional petrochemical-derived plastics. Nonnatural straight-chain amino acids, especially 5-aminovalerate, 6-aminocaproate and 7-aminoheptanoate are potential monomers for the synthesis of polymeric bioplastics as the...
| Main Authors: | , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
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Elsevier BV
2020
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| Online Access: | https://hdl.handle.net/1721.1/124917 |
| _version_ | 1811073960138244096 |
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| author | Torrens-Spence, Michael P. Weng, Jing-Ke |
| author2 | Whitehead Institute for Biomedical Research |
| author_facet | Whitehead Institute for Biomedical Research Torrens-Spence, Michael P. Weng, Jing-Ke |
| author_sort | Torrens-Spence, Michael P. |
| collection | MIT |
| description | Bioplastics produced from microbial source are promising green alternatives to traditional petrochemical-derived plastics. Nonnatural straight-chain amino acids, especially 5-aminovalerate, 6-aminocaproate and 7-aminoheptanoate are potential monomers for the synthesis of polymeric bioplastics as their primary amine and carboxylic acid are ideal functional groups for polymerization. Previous pathways for 5-aminovalerate and 6-aminocaproate biosynthesis in microorganisms are derived from L-lysine catabolism and the citric acid cycle, respectively. Here, we show the construction of an artificial iterative carbon-chain-extension cycle in Escherichia coli for simultaneous production of a series of nonnatural amino acids with varying chain length. Overexpression of L-lysine α-oxidase in E. coli yields 2-keto-6-aminocaproate (2K6AC) as a non-native substrate for the artificial iterative carbon-chain-extension cycle. The chain-extended α-ketoacid products are decarboxylated and oxidized by an α-ketoacid decarboxylase and an aldehyde dehydrogenase, respectively, to yield their corresponding nonnatural straight-chain amino acids. The engineered system demonstrated simultaneous in vitro production of 99.16 mg/L of 5-aminovalerate, 46.96 mg/L of 6-aminocaproate and 4.78 mg/L of 7-aminoheptanoate after 8 h of enzyme catalysis starting from 2K6AC as the substrate. Furthermore, simultaneous production of 2.15 g/L of 5-aminovalerate, 24.12 mg/L of 6-aminocaproate and 4.74 mg/L of 7-aminoheptanoate was achieved in engineered E. coli. This work illustrates a promising metabolic-engineering strategy to access other medium-chain organic acids with –NH2, –SCH3, –SOCH3, –SH, –COOH, –COH, or –OH functional groups through carbon-chain-elongation chemistry. |
| first_indexed | 2024-09-23T09:40:52Z |
| format | Article |
| id | mit-1721.1/124917 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T09:40:52Z |
| publishDate | 2020 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1249172022-09-26T13:04:14Z Production of nonnatural straight-chain amino acid 6-aminocaproate via an artificial iterative carbon-chain-extension cycle Torrens-Spence, Michael P. Weng, Jing-Ke Whitehead Institute for Biomedical Research Massachusetts Institute of Technology. Department of Biology Bioplastics produced from microbial source are promising green alternatives to traditional petrochemical-derived plastics. Nonnatural straight-chain amino acids, especially 5-aminovalerate, 6-aminocaproate and 7-aminoheptanoate are potential monomers for the synthesis of polymeric bioplastics as their primary amine and carboxylic acid are ideal functional groups for polymerization. Previous pathways for 5-aminovalerate and 6-aminocaproate biosynthesis in microorganisms are derived from L-lysine catabolism and the citric acid cycle, respectively. Here, we show the construction of an artificial iterative carbon-chain-extension cycle in Escherichia coli for simultaneous production of a series of nonnatural amino acids with varying chain length. Overexpression of L-lysine α-oxidase in E. coli yields 2-keto-6-aminocaproate (2K6AC) as a non-native substrate for the artificial iterative carbon-chain-extension cycle. The chain-extended α-ketoacid products are decarboxylated and oxidized by an α-ketoacid decarboxylase and an aldehyde dehydrogenase, respectively, to yield their corresponding nonnatural straight-chain amino acids. The engineered system demonstrated simultaneous in vitro production of 99.16 mg/L of 5-aminovalerate, 46.96 mg/L of 6-aminocaproate and 4.78 mg/L of 7-aminoheptanoate after 8 h of enzyme catalysis starting from 2K6AC as the substrate. Furthermore, simultaneous production of 2.15 g/L of 5-aminovalerate, 24.12 mg/L of 6-aminocaproate and 4.74 mg/L of 7-aminoheptanoate was achieved in engineered E. coli. This work illustrates a promising metabolic-engineering strategy to access other medium-chain organic acids with –NH2, –SCH3, –SOCH3, –SH, –COOH, –COH, or –OH functional groups through carbon-chain-elongation chemistry. Fundamental Research Funds for the Central Universities of China (Project 106112017CDJXFLX0014) Fundamental Research Funds for the Central Universities of China (Project 2018CDQYHG0010) Tianjin University. Science and Technology Support Program (Grant 15PTCYSY00020) Chinese Academy of Sciences. Research Equipment Program (Grant (YJKYYQ20170023) Chinese Academy of Sciences. Henan Provincial Science and Technology Open Cooperation Project (162106000014) 2020-04-29T12:10:21Z 2020-04-29T12:10:21Z 2019-09 2020-02-03T20:04:47Z Article http://purl.org/eprint/type/JournalArticle 1096-7176 https://hdl.handle.net/1721.1/124917 Cheng, Jie et al. “Production of nonnatural straight-chain amino acid 6-aminocaproate via an artificial iterative carbon-chain-extension cycle.” Metabolic Engineering 55 (2019): 23-32 © 2019 The Author(s) en 10.1016/j.ymben.2019.06.009 Metabolic Engineering Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV Other repository |
| spellingShingle | Torrens-Spence, Michael P. Weng, Jing-Ke Production of nonnatural straight-chain amino acid 6-aminocaproate via an artificial iterative carbon-chain-extension cycle |
| title | Production of nonnatural straight-chain amino acid 6-aminocaproate via an artificial iterative carbon-chain-extension cycle |
| title_full | Production of nonnatural straight-chain amino acid 6-aminocaproate via an artificial iterative carbon-chain-extension cycle |
| title_fullStr | Production of nonnatural straight-chain amino acid 6-aminocaproate via an artificial iterative carbon-chain-extension cycle |
| title_full_unstemmed | Production of nonnatural straight-chain amino acid 6-aminocaproate via an artificial iterative carbon-chain-extension cycle |
| title_short | Production of nonnatural straight-chain amino acid 6-aminocaproate via an artificial iterative carbon-chain-extension cycle |
| title_sort | production of nonnatural straight chain amino acid 6 aminocaproate via an artificial iterative carbon chain extension cycle |
| url | https://hdl.handle.net/1721.1/124917 |
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