Increased production of terpenes and terpenoids

A method for producing a terpene or a terpenoid in a recombinant host cell, comprising culturing the recombinant host cell under conditions wherein the terpene or terpenoid is produced in the recombinant host cell, wherein the recombinant host cell is genetically engineered to produce reduced expression of an endogenous farnesyl diphosphate (FPP) synthase, an endogenous geranyl diphosphate (GPP) synthase or an endogenous enzyme having both FPP synthase and GPP synthase activity compared to a non-engineered host cell;

• wherein reduced expression is produced in the recombinant host cell by:
• (a) introducing into the recombinant host cell a heterologous genetic construct encoding the endogenous FPP synthase, the endogenous GPP synthase, or the endogenous enzyme having both FPP synthase and GPP synthase activity operably linked to an exogenous weak promoter, wherein the weak promoter is KEX2, PGK-1, GPD1, ADH1, ADH2, PYK1, TPi1, PDC1, TEF1, TEF2, FBA1, GAL1-10, CUP1, MET2, MET14, MET25, CYC1, GAL1-S, GAL1-L, TEF1, CAG, CMV, human UbiC, RSV, EF-1alpha, SV40, Mt1, Tet-On, Tet-Off, Mo-MLV-LTR, Mx1, progesterone, RU486 or Rapamycin-inducible promoter;
• (b) introducing into the recombinant host cell a heterologous genetic construct encoding the endogenous FPP synthase, the endogenous GPP synthase, or the endogenous enzyme having both FPP synthase and GPP synthase activity operably linked to a messenger RNA destabilizing motif, comprising a M1 motif of SEQ ID NO:28 and/or a M24 motif of SEQ ID NO:29;
• or
• (c) introducing into the recombinant host cell a recombinant genetic construct, the construct comprising a gene encoding the endogenous FPP synthase, the endogenous GPP synthase, or the endogenous enzyme having both FPP synthase and GPP synthase activity operably linked to an endogenous promoter, wherein between the endogenous promoter and the gene encoding the endogenous FPP synthase, the endogenous GPP synthase, or the endogenous enzyme having both FPP synthase and GPP synthase activity is a heterologous insert sequence having the formula:
• -X1-X2-X3-X4-X5-;
• wherein X2 comprises at least 4 consecutive nucleotides being complementary to, and forming a hairpin secondary structure element with at least 4 consecutive nucleotides of X4;
• wherein X3 either comprises zero nucleotides or one or more unpaired nucleotides forming a hairpin loop between X2 and X4;
• wherein X4 comprises at least 4 consecutive nucleotides being complementary to, and forming a hairpin secondary structure element with at least 4 consecutive nucleotides of X2;
• and
• wherein X1 and X5 comprise zero, one or more nucleotides
• wherein the recombinant host cell further comprises one or more recombinant expression constructs encoding heterologous enzymes for producing said terpene or terpenoid;
• and
• wherein the recombinant host cell further comprises a recombinant expression construct encoding a truncated version of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGR), comprising the catalytically active carboxyl terminal portion thereof, comprising a region from amino acid 619 to amino acid 1025 of SEQ ID NO:8 and having at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:8.