Engineering an Alcohol-Forming Fatty Acyl-CoA Reductase for Aldehyde and Hydrocarbon Biosynthesis in Saccharomyces cerevisiae
Aldehydes are a class of highly versatile chemicals that can undergo a wide range of chemical reactions and are in high demand as starting materials for chemical manufacturing. Biologically, fatty aldehydes can be produced from fatty acyl-CoA by the action of fatty acyl-CoA reductases. The aldehydes...
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Frontiers Media S.A.
2020-10-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fbioe.2020.585935/full |
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| author | Jee Loon Foo Jee Loon Foo Bahareh Haji Rasouliha Bahareh Haji Rasouliha Adelia Vicanatalita Susanto Adelia Vicanatalita Susanto Susanna Su Jan Leong Susanna Su Jan Leong Susanna Su Jan Leong Matthew Wook Chang Matthew Wook Chang |
| author_facet | Jee Loon Foo Jee Loon Foo Bahareh Haji Rasouliha Bahareh Haji Rasouliha Adelia Vicanatalita Susanto Adelia Vicanatalita Susanto Susanna Su Jan Leong Susanna Su Jan Leong Susanna Su Jan Leong Matthew Wook Chang Matthew Wook Chang |
| author_sort | Jee Loon Foo |
| collection | DOAJ |
| description | Aldehydes are a class of highly versatile chemicals that can undergo a wide range of chemical reactions and are in high demand as starting materials for chemical manufacturing. Biologically, fatty aldehydes can be produced from fatty acyl-CoA by the action of fatty acyl-CoA reductases. The aldehydes produced can be further converted enzymatically to other valuable derivatives. Thus, metabolic engineering of microorganisms for biosynthesizing aldehydes and their derivatives could provide an economical and sustainable platform for key aldehyde precursor production and subsequent conversion to various value-added chemicals. Saccharomyces cerevisiae is an excellent host for this purpose because it is a robust organism that has been used extensively for industrial biochemical production. However, fatty acyl-CoA-dependent aldehyde-forming enzymes expressed in S. cerevisiae thus far have extremely low activities, hence limiting direct utilization of fatty acyl-CoA as substrate for aldehyde biosynthesis. Toward overcoming this challenge, we successfully engineered an alcohol-forming fatty acyl-CoA reductase for aldehyde production through rational design. We further improved aldehyde production through strain engineering by deleting competing pathways and increasing substrate availability. Subsequently, we demonstrated alkane and alkene production as one of the many possible applications of the aldehyde-producing strain. Overall, by protein engineering of a fatty acyl-CoA reductase to alter its activity and metabolic engineering of S. cerevisiae, we generated strains with the highest reported cytosolic aliphatic aldehyde and alkane/alkene production to date in S. cerevisiae from fatty acyl-CoA. |
| first_indexed | 2024-12-13T13:56:32Z |
| format | Article |
| id | doaj.art-f9c13df89b434bf7ba1d5c2a8fad8f66 |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-12-13T13:56:32Z |
| publishDate | 2020-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-f9c13df89b434bf7ba1d5c2a8fad8f662022-12-21T23:42:54ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852020-10-01810.3389/fbioe.2020.585935585935Engineering an Alcohol-Forming Fatty Acyl-CoA Reductase for Aldehyde and Hydrocarbon Biosynthesis in Saccharomyces cerevisiaeJee Loon Foo0Jee Loon Foo1Bahareh Haji Rasouliha2Bahareh Haji Rasouliha3Adelia Vicanatalita Susanto4Adelia Vicanatalita Susanto5Susanna Su Jan Leong6Susanna Su Jan Leong7Susanna Su Jan Leong8Matthew Wook Chang9Matthew Wook Chang10Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeNUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore, SingaporeDepartment of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeNUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore, SingaporeDepartment of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeNUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore, SingaporeDepartment of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeNUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore, SingaporeSingapore Institute of Technology, Singapore, SingaporeDepartment of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeNUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore, SingaporeAldehydes are a class of highly versatile chemicals that can undergo a wide range of chemical reactions and are in high demand as starting materials for chemical manufacturing. Biologically, fatty aldehydes can be produced from fatty acyl-CoA by the action of fatty acyl-CoA reductases. The aldehydes produced can be further converted enzymatically to other valuable derivatives. Thus, metabolic engineering of microorganisms for biosynthesizing aldehydes and their derivatives could provide an economical and sustainable platform for key aldehyde precursor production and subsequent conversion to various value-added chemicals. Saccharomyces cerevisiae is an excellent host for this purpose because it is a robust organism that has been used extensively for industrial biochemical production. However, fatty acyl-CoA-dependent aldehyde-forming enzymes expressed in S. cerevisiae thus far have extremely low activities, hence limiting direct utilization of fatty acyl-CoA as substrate for aldehyde biosynthesis. Toward overcoming this challenge, we successfully engineered an alcohol-forming fatty acyl-CoA reductase for aldehyde production through rational design. We further improved aldehyde production through strain engineering by deleting competing pathways and increasing substrate availability. Subsequently, we demonstrated alkane and alkene production as one of the many possible applications of the aldehyde-producing strain. Overall, by protein engineering of a fatty acyl-CoA reductase to alter its activity and metabolic engineering of S. cerevisiae, we generated strains with the highest reported cytosolic aliphatic aldehyde and alkane/alkene production to date in S. cerevisiae from fatty acyl-CoA.https://www.frontiersin.org/article/10.3389/fbioe.2020.585935/fullsynthetic biologymetabolic engineeringprotein engineeringde novo biosynthesisbiofuelsaldehydes |
| spellingShingle | Jee Loon Foo Jee Loon Foo Bahareh Haji Rasouliha Bahareh Haji Rasouliha Adelia Vicanatalita Susanto Adelia Vicanatalita Susanto Susanna Su Jan Leong Susanna Su Jan Leong Susanna Su Jan Leong Matthew Wook Chang Matthew Wook Chang Engineering an Alcohol-Forming Fatty Acyl-CoA Reductase for Aldehyde and Hydrocarbon Biosynthesis in Saccharomyces cerevisiae Frontiers in Bioengineering and Biotechnology synthetic biology metabolic engineering protein engineering de novo biosynthesis biofuels aldehydes |
| title | Engineering an Alcohol-Forming Fatty Acyl-CoA Reductase for Aldehyde and Hydrocarbon Biosynthesis in Saccharomyces cerevisiae |
| title_full | Engineering an Alcohol-Forming Fatty Acyl-CoA Reductase for Aldehyde and Hydrocarbon Biosynthesis in Saccharomyces cerevisiae |
| title_fullStr | Engineering an Alcohol-Forming Fatty Acyl-CoA Reductase for Aldehyde and Hydrocarbon Biosynthesis in Saccharomyces cerevisiae |
| title_full_unstemmed | Engineering an Alcohol-Forming Fatty Acyl-CoA Reductase for Aldehyde and Hydrocarbon Biosynthesis in Saccharomyces cerevisiae |
| title_short | Engineering an Alcohol-Forming Fatty Acyl-CoA Reductase for Aldehyde and Hydrocarbon Biosynthesis in Saccharomyces cerevisiae |
| title_sort | engineering an alcohol forming fatty acyl coa reductase for aldehyde and hydrocarbon biosynthesis in saccharomyces cerevisiae |
| topic | synthetic biology metabolic engineering protein engineering de novo biosynthesis biofuels aldehydes |
| url | https://www.frontiersin.org/article/10.3389/fbioe.2020.585935/full |
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