3-hydroxyisovalerate (HIV) synthase variants

A 3-hydroxyisovalerate (HIV) synthase variant showing an improved activity in converting acetone and a compound which provides an activated acetyl group characterized by the following formula (I):

• into 3-hydroxyisovalerate over the corresponding HIV synthase from which it is derived, wherein X is selected from the group consisting of S—CH2-CH2-NH—CO—CH2-CH2-NH—CO—CH(OH)—C(CH3)2-CH2-O—PO2H—O—PO2H—C10H13N5O7P (coenzyme A), S—CH2-CH2-NH—CO—CH2-CH2-NH—CO—CH(OH)—C(CH3)2-CH2-O—PO2H-polypeptide (acyl-carrier protein), S—CH2-CH2-NH—CO—CH2-CH2-NH—CO—CH(OH)—C(CH3)2-CH2-OH (pantetheine), S—CH2-CH2-NH—CO—CH3 (N-acetyl-cysteamine), S—CH3 (methane thiol), S—CH2-CH(NH2)-CO2H (cysteine), S—CH2-CH2-CH(NH2)-CO2H (homocysteine), S—CH2-CH(NH—C5H8NO3)-CO—NH—CH2-CO2H (glutathione), S—CH2-CH2-SO3H (coenzyme M) and OH (acetic acid), and wherein the HIV synthase variant is derived from the amino acid sequence as shown in SEQ ID NO:1 or an amino acid sequence having at least 80% sequence identity to SEQ ID NO:1, and in which the HIV synthase variant comprises one or more amino acid residues at a position selected from the group consisting of:
• (1) an amino acid residue at position 33 in the amino acid sequence shown in SEQ ID NO:1 or at a position corresponding to this position in the sequence from which the HIV synthase variant is derived, is substituted;
• and/or
• (2) an amino acid residue at position 74 in the amino acid sequence shown in SEQ ID NO:1 or at a position corresponding to this position in the sequence from which the HIV synthase variant is derived, is deleted or substituted;
• and/or
• (3) an amino acid residue at position 171 in the amino acid sequence shown in SEQ ID NO:1 or at a position corresponding to this position in the sequence from which the HIV synthase variant is derived, is substituted;
• and/or
• (4) an amino acid residue at position 221 in the amino acid sequence shown in SEQ ID NO:1 or at a position corresponding to this position in the sequence from which the HIV synthase variant is derived, is deleted or substituted;
• and/or
• (5) an amino acid residue at position 222 in the amino acid sequence shown in SEQ ID NO:1 or at a position corresponding to this position in the sequence from which the HIV synthase variant is derived, is deleted or substituted;
• and/or
• (6) an amino acid residue at position 338 in the amino acid sequence shown in SEQ ID NO:1 or at a position corresponding to this position in the sequence from which the HIV synthase variant is derived, is deleted or substituted;
• and/or
• (7) an amino acid residue at position 345 in the amino acid sequence shown in SEQ ID NO:1 or at a position corresponding to this position in the sequence from which the HIV synthase variant is derived, is deleted or substituted;
• and/or
• (8) an amino acid residue at position 394 in the amino acid sequence shown in SEQ ID NO:1 or at a position corresponding to this position in the sequence from which the HIV synthase variant is derived, is deleted or substituted;
• and/or
• (9) an amino acid residue at position 396 in the amino acid sequence shown in SEQ ID NO:1 or at a position corresponding to this position in the sequence from which the HIV synthase variant is derived, is substituted.