BioChem - DOS

Engineered Production of Short-Chain Acyl-Coenzyme A Esters in Saccharomyces cerevisiae

ACS Synthetic biology

Krink-Koutsoubelis, Nicolas; Loechner, Anne C.; Lechner, Anna; Link, Hannes; Denby, Charles M.; Vö geli, Bastian; Erb, Tobias J.; Yuzawa, Satoshi; Jakociunas, Tadas; Katz, Leonard; Jensen, Michael K.; Sourjik, Victor; Keasling, Jay D.

<P>Short-chain acyl-coenzyme A esters serve as intermediate compounds in fatty acid biosynthesis, and the production of polyketides, biopolymers and other value-added chemicals. <I>S. cerevisiae</I> is a model organism that has been utilized for the biosynthesis of such biologically and economically valuable compounds. However, its limited repertoire of short-chain acyl-CoAs effectively prevents its application as a production host for a plethora of natural products. Therefore, we introduced biosynthetic metabolic pathways to five different acyl-CoA esters into <I>S. cerevisiae</I>. Our engineered strains provide the following acyl-CoAs: propionyl-CoA, methylmalonyl-CoA, <I>n</I>-butyryl-CoA, isovaleryl-CoA and <I>n</I>-hexanoyl-CoA. We established a yeast-specific metabolite extraction protocol to determine the intracellular acyl-CoA concentrations in the engineered strains. Propionyl-CoA was produced at 4-9 &mu;M; methylmalonyl-CoA at 0.5 &mu;M; and isovaleryl-CoA, <I>n</I>-butyryl-CoA, and <I>n</I>-hexanoyl-CoA at 6 &mu;M each. The acyl-CoAs produced in this study are common building blocks of secondary metabolites and will enable the engineered production of a variety of natural products in <I>S. cerevisiae</I>. By providing this toolbox of acyl-CoA producing strains, we have laid the foundation to explore <I>S. cerevisiae</I> as a heterologous production host for novel secondary metabolites.</P><BR>[FIG OMISSION]</BR>

2018

American Chemical Society

2161-5063

7

4

pp.1105-1115

10.1021/acssynbio.7b00466.s001

http://click.ndsl.kr/servlet/OpenAPIDetailView?keyValue=05787966&target=NART&cn=NART91802458

https://doi.org/10.1021/acssynbio.7b00466.s001

metabolic engineering; S. cerevisiae; heterologous pathway; precursor engineering; platform molecules; acyl-coenzyme A