Natural　2-phenylethanol　(PEA)　could　be　produced　on　a　large　scale　by　way　of　bioconversion　with　yeast　from　L-phenylalanine.　In　this　work　the　synergistic　inhibition　effect　of　the　target　product　PEA　and　the　byproduct　ethanol　on　the　bioconversion　rate　by　Saccharomyces　cerevisiae　R-UV3　was　systematically　studied　and　a　new　kinetic　model　with　an　item　representing　the　synergistic　effect　was　proposed.　Optimization　strategies　to　repress　the　inhibition　effect　of　PEA　and　ethanol　were　carried　out　in　the　mode　of　fed-batch　culture　with　ISPR.　The　glucose　concentration　was　regulated　at　the　level　of　0.2　+/-　0.1　g/L　by　controlling　a　suitable　respiratory　quotient　on　line,　which　could　limit　the　accumulation　of　the　ethanol　lower　than　10　g/L　In　the　presence　of　resin　FD0816　with　a　weight　of　10%　of　the　medium,　PEA　was　removed　from　the　broth　and　the　overall　PEA　concentration　and　the　space-time　yield　reached　13.7　g/L　and　0.39　g　L(-1)　h(-1)　respectively.　The　semi-continuous　process　with　ISPR　was　performed,　in　which　the　replacement　of　the　resin　was　operated　repeatedly　when　the　aqueous　PEA　was　over　2.7　g/L　and　bioconversion　continued　until　the　bioactivity　of　the　yeast　cells　declined,　consequently　achieving　a　final　overall　PEA　concentration　of　32.5　g/L　and　a　space-time　yield　of　0.45　g　L(-1)　h(-1).　(C)　2011,　The　Society　for　Biotechnology,　Japan.　All　rights　reserved.