초록
<P><I>Escherichia coli</I> was engineered for the production of even- and odd-chain fatty acids (FAs) by fermentation. Co-production of thiolase, hydroxybutyryl-CoA dehydrogenase, crotonase and <I>trans</I>-enoyl-CoA reductase from a synthetic operon allowed the production of butyrate, hexanoate and octanoate. Elimination of native fermentation pathways by genetic deletion (Δ<I>ldhA</I>, Δ<I>adhE</I>, Δ<I>ackA</I>, Δ<I>pta</I>, Δ<I>frdC</I>) helped eliminate undesired by-products and increase product yields. Initial butyrate production rates were high (0.7 g l<SUP>−1</SUP> h<SUP>−1</SUP>) but quickly levelled off and further study suggested this was due to product toxicity and/or acidification of the growth medium. Results also showed that endogenous thioesterases significantly influenced product formation. In particular, deletion of the <I>yciA</I> thioesterase gene substantially increased hexanoate production while decreasing the production of butyrate. <I>E. coli</I> was also engineered to co-produce enzymes for even-chain FA production (described above) together with a coenzyme B<SUB>12</SUB>-dependent pathway for the production of propionyl-CoA, which allowed the production of odd-chain FAs (pentanoate and heptanoate). The B<SUB>12</SUB>-dependent pathway used here has the potential to allow the production of odd-chain FAs from a single growth substrate (glucose) in a more energy-efficient manner than the prior methods.</P>