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.

中文翻译：

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在酿酒酵母中设计用于醛和烃生物合成的生成醇的脂肪酰基辅酶 A 还原酶

醛是一类用途广泛的化学品，可以进行广泛的化学反应，并且作为化学制造的原材料需求量很大。在生物学上，脂肪醛可以通过脂肪酰基辅酶A还原酶的作用从脂肪酰基辅酶A产生。产生的醛可以进一步通过酶促转化为其他有价值的衍生物。因此，用于生物合成醛及其衍生物的微生物代谢工程可以为关键的醛前体生产和随后转化为各种增值化学品提供经济和可持续的平台。酿酒酵母是用于此目的的极好宿主，因为它是一种健壮的生物体，已广泛用于工业生化生产。然而，迄今为止，在酿酒酵母中表达的脂肪酰基辅酶A依赖性醛形成酶的活性极低，因此限制了脂肪酰基辅酶A作为醛生物合成底物的直接利用。为了克服这一挑战，我们通过合理的设计成功地设计了一种用于醛生产的酒精形成脂肪酰基辅酶A还原酶。我们通过删除竞争途径和增加底物可用性，通过菌株工程进一步提高了醛的产量。随后，我们证明了烷烃和烯烃的生产是醛生产菌株的许多可能应用之一。总的来说，通过脂肪酰基辅酶A还原酶的蛋白质工程改变其活性和酿酒酵母的代谢工程，