Synthesis of non-natural cofactor analogs of S-adenosyl-L-methionine using methionine adenosyltransferase

Patent metadata

Field	Value
Publication number	US-9879043-B1
Application number	US-201414298874-A
Country	US
Kind code	B1
Filing date	Jun 6, 2014
Priority date	Jun 6, 2013
Publication date	Jan 30, 2018
Grant date	Jan 30, 2018

Abstract

The present disclosure relates to the synthesis of non-natural analogs of S-adenosyl-L-methionine (SAM) and/or of Se-adenosyl-L-methionine (SeAM) by reacting a methionine analog and adenosine triphosphate (ATP) in the presence of at least one methionine adenosyltransferase (MAT), and to use thereof with downstream SAM and/or SeAM utilizing enzymes. The non-natural analogs of SAM and/or SeAM have the general formula:

where X is S or Se, and R 1 is an alkyl group.

First claim

What is claimed is:

1. An S-adenosyl-L-methionine (SAM) or Se-adenosyl-L-methionine (SeAM) analog of the Formula III:

wherein X is selected from the group consisting of S and Se;
wherein, when X is S, R 1 is selected from the group consisting of:

wherein, when X is Se, R 1 is selected from the group consisting of:

2. A compound of the Formula II:

wherein R 1 is selected from the group consisting of

and X is S.

3. An S-adenosyl-L-methionine analog of the Formula III:

wherein X is S and R 1 is selected from the group consisting of:

4. An S-adenosyl-L-methionine (SAM) analog of the formula:

5. A method of producing an S-adenosyl-L-methionine analog according to claim 4 , comprising the step of reacting a first substrate comprising methionine-tetrazole with a second substrate comprising adenosine triphosphate (ATP) in the presence of a methionine adenosyltransferase (MAT).

6. The method of claim 5 , wherein the MAT comprises at least one of human MAT II catalytic alpha and regulatory beta subunit (hMAT2), human MAT II catalytic alpha subunit alone (hMAT2A), human MAT I catalytic subunit alpha (hMAT1A), Escherichia coli MAT (eMAT), Sulfolobus solfataricus MAT (sMAT), and Methanocaldococcus jannaschii MAT (mMAT).

7. A method of producing the S-adenosyl-L-methionine analog of claim 1 , comprising the step of reacting a first substrate comprising a methionine analog with a second substrate comprising adenosine triphosphate (ATP) in the presence of a methionine adenosyltransferase (MAT).

8. The method of claim 7 , wherein the MAT comprises at least one of human MAT II catalytic alpha and regulatory beta subunit (hMAT2), human MAT II catalytic alpha subunit alone (hMAT2A), human MAT I catalytic subunit alpha (hMAT1A), Escherichia coli MAT (eMAT), Sulfolobus solfataricus MAT (sMAT), and Methanocaldococcus jannaschii MAT (mMAT).

9. The method of claim 7 , wherein the first substrate is of the Formula II:

wherein R 1 is selected from the group consisting of

wherein X is S.

10. A method of producing the Se-adenosyl-L-methionine analog of claim 1 , comprising the step of reacting a first substrate comprising a methionine analog with a second substrate comprising adenosine triphosphate (ATP) in the presence of a methionine adenosyltransferase (MAT).

11. The method of claim 10 , wherein the first substrate is of the Formula II:

wherein R 1 is selected from the group consisting of

wherein X is Se.

12. A method of producing an indolocarbazole analog, comprising the step of reacting a first substrate comprising a methionine analog with a second substrate in the presence of a methionine adenosyltransferase (MAT), wherein the methionine analog is of the Formula II:

wherein R 1 is selected from the group consisting of

wherein X is selected from the group consisting of S and Se; and
wherein the second substrate comprises at least one indolocarbazole group.

13. The method of claim 12 , wherein the MAT comprises at least one of human MAT II catalytic alpha and regulatory beta subunit (hMAT2), human MAT II catalytic alpha subunit alone (hMAT2A), human MAT I catalytic subunit alpha (hMAT1A), Escherichia coli MAT (eMAT), Sulfolobus solfataricus MAT (sMAT), and Methanocaldococcus jannaschii MAT (mMAT).

Assignees

• Univ Kentucky Res Found

Inventors

• Thorson Jon
• Huber Tyler
• Zhang Jianjun
• Singh Shanteri

Classifications

• C12P17/188

  Heterocyclic compound containing in the condensed system at least one hetero ring having nitrogen atoms and oxygen atoms as the only ring heteroatoms (ergot-alcaloids C12P17/183) · CPC title

• C12P19/40

  having a condensed ring system containing a six-membered ring having two nitrogen atoms in the same ring, e.g. purine nucleosides · CPC title

• C07H19/16 Primary

  Purine radicals · CPC title

• C07D405/14

  containing three or more hetero rings · CPC title

• C07C321/04

  of an acyclic saturated carbon skeleton · CPC title