Engineering an Alcohol-Forming Fatty Acyl-CoA Reductase for Aldehyde and Hydrocarbon Biosynthesis in Saccharomyces cerevisiae .

Autor: Foo JL; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore, Singapore., Rasouliha BH; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore, Singapore., Susanto AV; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore, Singapore., Leong SSJ; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore, Singapore.; Singapore Institute of Technology, Singapore, Singapore., Chang MW; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore, Singapore.
Jazyk: angličtina
Zdroj: Frontiers in bioengineering and biotechnology [Front Bioeng Biotechnol] 2020 Oct 06; Vol. 8, pp. 585935. Date of Electronic Publication: 2020 Oct 06 (Print Publication: 2020).
DOI: 10.3389/fbioe.2020.585935
Abstrakt: 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.
(Copyright © 2020 Foo, Rasouliha, Susanto, Leong and Chang.)
Databáze: MEDLINE