In recent years,
production of fatty acid derivatives has attracted
much attention because of their wide range of applications in renewable
oleochemicals. Microorganisms such as Saccharomyces
cerevisiae provided an ideal cell factory for such
chemical synthesis. In this study, an efficient strategy for the synthesis
of fatty alcohols based on enhanced supply of free fatty acids (FFAs)
was constructed. The FAA1 and FAA4 genes encoding two acyl-CoA synthetases in S. cerevisiae were deleted, resulting in the accumulation of FFAs with carbon
chain length from C8 to C18. The coexpression of the carboxylic acid
reductase gene (car) from Mycobacterium
marinum and the phosphopantetheinyl transferase gene
(sfp) from Bacillus subtilis successfully converted the accumulated FFAs into fatty alcohols.
The concentration of the total fatty alcohols reached 24.3 mg/L, which
is in agreement with that of the accumulated FFAs. To further increase
the supply of FFAs, the DGAI encoding the acyl-CoA:diacylglycerol
acyltransferase involved in the rate-limiting step of triacylglycerols
storage was codeleted with FAA1 and FAA4, and the acyl-CoA thioesterase gene (acot) was
expressed together with car and sfp, resulting in an enhanced production of fatty alcohols, the content
of which increased to 31.2 mg/L. The results herein demonstrated the
efficiency of the engineered pathway for the production of fatty acid
derivatives using FFAs as precursors.
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