Abstract
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.
Highlights
Fatty aldehydes are a class of compounds with a wide range of applications, such as fragrances and flavorings (Kohlpaintner et al, 2013)
The C-terminal domain possibly contributes to the fatty acylCoA reductase (FACR) activity of maFACR for aldehyde biosynthesis from fatty acyl-CoA
Since maFACR is an alcohol-forming FACR, it is hypothesized that the N-terminal domain functions as an aldehyde reductase to convert the aldehyde intermediate to alcohol, this domain has only low homology to a known fatty aldehyde reductase (FALDR) (Willis et al, 2011)
Summary
Fatty aldehydes are a class of compounds with a wide range of applications, such as fragrances and flavorings (Kohlpaintner et al, 2013). Fatty aldehydes can be biosynthesized under ambient conditions from fatty acids or their acyl-CoA forms via enzymatic reactions in biological systems (Reiser and Somerville, 1997; Koeduka et al, 2002; Schirmer et al, 2010; Akhtar et al, 2013). The aldehydes could serve as precursors to concurrently produce their derivatives in vivo via other metabolic pathways (Schirmer et al, 2010; Jin et al, 2016; Ladkau et al, 2016). By introducing synthetic metabolic pathways, the aldehydes formed could serve as substrates for conversion to a variety of valuable chemicals
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