Producing 3-hydroxycarboxylic acid and ketone using polyketide synthases

1. A non-naturally occurring polyketide synthase (PKS) capable of synthesizing a 3-hydroxycarboxylic acid or ketone; wherein the PKS comprises a loading acyltransferase (ATL) domain and a loading ACP (ACP L ) domain, both of LipPk1 of a lipomycin synthase of Streptomyces aureofaciens T0117, a ketosynthase (KS) domain, an acyltransferase (AT) domain, a ketoreductase (KR) domain, an ACP domain of LipPks1 of a lipomycin synthase of Streptomyces aureofaciens Tü117, and a thioesterase (TE) domain appended to the C-terminus of the ACP domain of LipPks1;

wherein (a) the AT domain is an AT domain from module 1 of borrelidin PKS, (b) the KR domain is a mutated KR domain being a KR domain of LipPks1 of a lipomycin synthase of Streptomyces aureofaciens Tü117 having an active-site scrims residue mutated to alanine such that the amino add sequence of SEQ ID NO: 7 comprised in the KR domain of LipPks1 is mutated to SEQ ID NO: 9 in the mutated KR domain, or both (a) and (b).

2. The PKS of claim 1 , wherein the PKS is a hybrid PKS comprising modules, domains, and/or portions thereof from two or more PKSs.

3. The PKS of claim 1 , wherein the 3 -hydroxycarboxylic acid has the following chemical structure:

wherein R 1 is —H, R 2 is —H, —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH(CH 3 ) 2 , —CH(CH 3 )CH 2 CH 3 , —CH 2 CH(CH 3 ) 2 , —C 6 H 11 , or —C 6 H 5 , and R 3 is —H, —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 Cl, —CH 2 CH═CH 2 , or —CH 2 CH 2 COCH 3 .

4. The PKS of claim 1 , wherein the ketone has the following chemical structure:

wherein each R is —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH(CH 3 ) 2 , —CH(CH 3 )CH 2 CH 3 , —CH 2 CH(CH 3 ) 2 , —C 6 H 11 , or —C 6 H 5 , and each R′ is —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 Cl, —CH 2 CH═CH 2 , or —CH 2 CH 2 COCH 3 .

5. A recombinant nucleic acid encoding the polyketide synthase (PKS) of claim 1 .

6. A host cell comprising the recombinant nucleic acid of claim 5 .

7. The host cell of claim 6 , wherein the host cell when cultured produces the 3-hydroxycarboxylic acid or ketone.

8. A replicon comprising the recombinant nucleic acid 7 , wherein the replicon is capable of stable maintenance in a host cell.

9. The replicon of claim 8 , wherein the replicon is a plasmid or vector.

10. The replicon of claim 9 , wherein the vector is an expression vector.

11. A host cell comprising the replicon of claim 8 .

12. A method of producing a 3-hydroxycarboxylic acid or ketone, comprising: providing a host cell of claim 11 , and culturing said host cell in a suitable culture medium such that the 3-hydroxycarboxylic acid or ketone is produced.

13. The method of claim 12 , further comprising isolating the 3-hydroxycarboxylic acid or ketone.