Session 6

Leber at al., (2013). Engineering of Saccharomyces cerevisiae for the Synthesis of Short Chain Fatty Acids.

Key findings:

The introduction of human Fatty acid synthase (FAS) and exogenous short chain thioesterases in S. cerevisiae increased in vivo caprylic acid (octanoic acid) and total SCFA production up to 64-fold (63 mg/L) and 52-fold (68mg/L). Combined over-expression of the phosphopantetheine transferase (PPT) with the human FAS mutant resulted in octanoic acid titers of up to 82 mg/L and total SCFA titers of up to 111 mg/L. No significant improves were shown in the production of caproic acid (hexanoic acid).

In this publication it was also demonstrated the functional replacement of the native fungal FAS by human FAS, an experiment in which human FAS was overexpressed in a FAS2 knockout strain (deficient in de novo fatty acid synthesis).

Relevance of the article:

This is the first report of an active mammalian FAS expressed in yeast and the first report of the in vivoproduction of SCFAs in S. cerevisiae.

S. cerevisiae.was engineered to produce SCFAs by introducing the human FAS and heterologous short chain thioesterases genes. Exogenous phosphopantetheine transfereases (PPTs) were expressed to create the active holo-hFAS form, and in vitro and in vivo activity of the hFAS was confirmed. The thioesterase domain was removed from hFAS to allow the premature cleaving of the elongating fatty acids by independent or linked exogeneous short chain TEs and the production of SCFAs was demonstrated.

Rating (‘Exceptional – a must read paper’, ‘Very good – worth spending the time’, ‘Good – only if you have time to spare’).

Very good paper.

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