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Background  Acetyl-CoA is an important precursor in  Saccharomyces cerevisiae . Various approaches have been adopted to improve its cytosolic level previously with the emphasis on engineering the “acetyl-” part of acetyl-CoA. To the best of our knowledge, there have been no reports on engineering the “-CoA” part so far.    Results  In this study, we had tried to engineer  S. cerevisiae  from both the “-CoA” part via pantothenate kinase overexpression (PanK from  S. cerevisiae , the rate-limiting enzyme for CoA synthesis) and the “acetyl-“part through PDH bypass introduction ( ALD6  from  S. cerevisiae  and Se Acs    L641P   from  Salmonella enteric ). A naringenin-producing reporter strain had been constructed to reflect cytosolic acetyl-CoA level as acetyl-CoA is the precursor of naringenin. It was found that PanK overexpression or PDH bypass introduction alone only led to a twofold or 6.74-fold increase in naringenin titer, but the combination of both (strain CENFPAA01) had resulted in 24.4-fold increase as compared to the control (strain CENF09) in the presence of 0.5 mM substrate  p -coumaric acid. The supplement of PanK substrate pantothenate resulted in another 19% increase in naringenin production.    Conclusions  To greatly enhance acetyl-CoA level in yeast cytosol, it is feasible to engineer both the “acetyl-” part and the “-CoA” part simultaneously. Insufficient CoA supply might aggravate acetyl-CoA shortage and cause low yield of target product.    Electronic supplementary material  The online version of this article (doi:10.1186/s13068-017-0726-z) contains supplementary material, which is available to authorized users.

Improving acetyl-CoA biosynthesis in Saccharomyces cerevisiae via the overexpression of pantothenate kinase and PDH bypass