Novel spinosyn-producing polyketide synthases
AssigneeDow AgroSciences LLC
InventorsLesley Burns, Paul Graupner, Paul Lewer, Christine Martin, William Vousden, Clive Waldron, Barrie Wilkinson
Life of this patent
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Abstract
The invention provides, biologically active spinosyns, hybrid spinosyn polyketide synthases capable of functioning in Saccharopolyspora spinosa to produce the spinosyns, and methods of controlling insects using the spinosyns.
Claims23
A compound of the formula (1)
- wherein
- R1 is hydrogen, methyl, or ethyl;
- R2 is hydrogen, methyl, or ethyl;
- R3 is hydrogen,
- R4 is methyl or ethyl, either of which may be substituted with one or more groups selected from halo, hydroxy, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylthio, or cyano;
- R4 is an alpha-branched C3-C5 alkyl group, C3-C8 cycloalkyl group, or C3-C8 cycloalkenyl group, any of which may be substituted with one or more groups selected from halo, hydroxy, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylthio, or cyano;
- or
- R4 is a 3-6 membered heterocyclic group that contains O or S, that is saturated or fully or partially unsaturated, and that may be substituted with one or more groups selected from halo, hydroxy, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylthio, or cyano;
- R5 is hydrogen or methyl;
- R6 is hydrogen or methyl;
- R7 is hydrogen or methyl;
- R8 is hydrogen, methyl, or ethyl;
- R9 is hydrogen, methyl, or ethyl;
- or a 5,6-dihydro derivative of a compound of formula I,
- provided that the compound has at least one of the following features:
- a) R4 is methyl or ethyl substituted with one or more groups selected from halo, hydroxy, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylthio, or cyano;
- or
- b) R4 is an alpha-branched C3-C5 alkyl group, C3-C8 cycloalkyl group, or C3-C8 cycloalkenyl group, any of which may be substituted with one or more groups selected from halo, hydroxy, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylthio, or cyano;
- or
- c) R4 is a 3-6 membered heterocyclic group that contains O or S, that is saturated or fully or partially unsaturated, and that may be substituted with one or more groups selected from halo, hydroxy, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylthio, or cyano;
- or
- d) R1 or R2 is ethyl;
- or
- e) R8 is methyl or ethyl;
- or
- f) R9 is methyl or ethyl.
A compound selected from the group consisting of:
- 21-desethyl-21-cyclopropyl spinosyn A;
- 21-desethyl-21-cyclopropyl spinosyn D;
- 21-desethyl-21-cyclobutyl spinosyn A;
- 21-desethyl-21-cyclobutyl spinosyn D;
- 21-desethyl-21-methylthiomethyl spinosyn A;
- 21-desethyl-21-methylthiomethyl spinosyn D;
- 21-desethyl-21-cyanomethyl spinosyn A;
- 5,6-dihydro-21-desethyl-21-cyclobutyl spinosyn A;
- 21-desethyl-21-isopropyl spinosyn A;
- 21-desethyl-21-isopropyl spinosyn D;
- 21-desethyl-21-sec-butyl spinosyn A;
- 21-desethyl-21-sec-butyl spinosyn D;
- 21-desethyl-21-methylcyclopropyl spinosyn A;
- 21-desethyl-21-methylcyclopropyl spinosyn D;
- 21-desethyl-21-(3-ffiryl) spinosyn A;
- 21-desethyl-21-(3-furyl) spinosyn D;
- 21-desethyl-21-cyclopropyl spinosyn A 17-pseudoaglycone;
- 21-desethyl-21-cyclopropyl spinosyn D 17-pseudoaglycone;
- 21-desethyl-21-cyclobutyl spinosyn A 17-pseudoaglycone;
- 21-desethyl-21-cyclobutyl spinosyn D 17-pseudoaglycone;
- 16-desmethyl spinosyn D;
- 16-desmethyl spinosyn D 17-pseudoaglycone;
- 21-desethyl-21-n-propyl spinosyn A;
- 6-ethyl spinosyn A;
- 6-ethyl-21-desethyl-21-n-propyl spinosyn A;
- 16-desmethyl-16-ethyl spinosyn A;
- 16-desmethyl-16-ethyl spinosyn D;
- and
- 21-desethyl-21-n-propyl spinosyn D.
A hybrid spinosyn polyketide synthase that is capable of functioning in Saccharopolyspora spinosa to produce a biologically active spinosyn, said hybrid polyketide synthase comprising a heterologous loading module operatively associated with a plurality of Saccharopolyspora spinosa extender modules.
A hybrid spinosyn polyketide synthase that is capable of functioning in Saccharopolyspora spinosa to produce a biologically active 16-ethyl spinosyn compound, said hybrid polyketide synthase being the product produced by spinosyn biosynthetic DNA modified so that the DNA for the AT domain of module 3 in the spinosyn PKS is replaced with DNA for an AT domain that normally incorporates ethyl malonyl-CoA.
A hybrid spinosyn polyketide synthase that is capable of functioning in Saccharopolyspora spinosa to produce a biologically active 18-ethyl spinosyn compound, said hybrid polyketide synthase being the product produced by spinosyn biosynthetic DNA modified so that the DNA for the AT domain of module 2 in the spinosyn PKS is replaced with DNA for an AT domain that normally incorporates ethyl malonyl-CoA.
A hybrid spinosyn polyketide synthase that is capable of functioning in Saccharopolyspora spinosa to produce a biologically active 20-ethyl spinosyn compound, said hybrid polyketide synthase being the product produced by spinosyn biosynthetic DNA modified so that the DNA for the AT domain of module 1 in the spinosyn PKS is replaced with DNA for an AT domain that normally incorporates ethyl malonyl-CoA.
A hybrid spinosyn polyketide synthase that is capable of functioning in Saccharopolyspora spinosa to produce a biologically active 16-ethyl spinosyn compound, 20-ethyl spinosyn compound, or 18-ethyl spinosyn compound, said hybrid polyketide synthase being the product produced by spinosyn biosynthetic DNA modified so that the DNA for the AT domain of module 3, module 2, or module 1 in the spinosyn PKS is replaced with DNA for the AT domain of module 5 in the tylosin PKS.
A hybrid spinosyn polyketide synthase that is capable of functioning in Saccharopolyspora spinosa to produce a biologically active 18-methyl spinosyn compound, said hybrid polyketide synthase being the product produced by spinosyn biosynthetic DNA modified so that the DNA for the AT domain of module 2 in the spinosyn PKS is replaced with DNA for an AT domain that normally incorporates methyl malonyl-CoA.
A hybrid spinosyn polyketide synthase that is capable of functioning in Saccharopolyspora spinosa to produce a biologically active 20-methyl spinosyn compound, said hybrid polyketide synthase being the product produced by spinosyn biosynthetic DNA modified so that the DNA for the AT domain of module 1 in the spinosyn PKS is replaced with DNA for an AT domain that normally incorporates methyl malonyl-CoA.
A process for producing a 6-ethyl spinosyn compound, a 21-desethyl-21-n-propyl spinosyn compound, or a 6-ethyl-21-desethyl-21-n-propyl spinosyn compound which comprises culturing a host organism that coexpresses crotonyl-CoA reductase with the spinosyn biosynthetic pathway.
An S. spinosa strain that has been transformed with DNA encoding the S. cinnamonensis crotonyl-CoA reductase.
A biologically pure culture of Saccharopolyspora spinosa selected from
- NRRL 30539,
- NRRL 30540,
- NRRL 30541, and
- NRRL 30542.
Dependencies are inferred from the claim text.