Expanding the Structural Diversity of Polyketides by Exploring the Cofactor Tolerance of an Inline Methyltransferase Domain

Details

• Alternative Title:
  Org Lett
• Personal Author:
  Winter, Jaclyn M. ; Chiou, Grace ; Bothwell, Ian R. ; Xu, Wei ; Garg, Neil K. ; Luo, Minkui ; Tang, Yi
• Description:
  A strategy for introducing structural diversity into polyketides by exploiting the promiscuity of an in-line methyltransferase domain in a multidomain polyketide synthase is reported. In vitro investigations using the highly-reducing fungal polyketide synthase CazF revealed that its methyltransferase domain accepts the nonnatural cofactor propargylic Se-adenosyl-l-methionine and can transfer the propargyl moiety onto its growing polyketide chain. This propargylated polyketide product can then be further chain-extended and cyclized to form propargyl-α pyrone or be processed fully into the alkyne-containing 4'-propargyl-chaetoviridin A.
• Subjects:
  Amino Acid Sequence Furans Methyltransferases Pargyline Polyketides Polyketide Synthases Protein Structure, Tertiary Pyrones
• Source:
  Org Lett. 15(14):3774-3777
• Pubmed ID:
  23837609
• Pubmed Central ID:
  PMC3779521
• Document Type:
  Journal Article
• Funding:
  R01 GM096056/GM/NIGMS NIH HHSUnited States/ ; DP1 GM106413/GM/NIGMS NIH HHSUnited States/ ; DP2 OD007335/OD/NIH HHSUnited States/ ; T32 GM008496/GM/NIGMS NIH HHSUnited States/ ; S10 RR025631/RR/NCRR NIH HHSUnited States/ ; S10RR025631/RR/NCRR NIH HHSUnited States/ ; 1DP2OD007335/OD/NIH HHSUnited States/ ; 1DP1GM106413/DP/NCCDPHP CDC HHSUnited States/ ; 1R01GM096056/GM/NIGMS NIH HHSUnited States/
• Volume:
  15
• Issue:
  14
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:95d0adf5be7d16056dc563d45523f04a3ad571b1704f70ea7e839f54fe44bea3
• Download URL:
  https://stacks.cdc.gov/view/cdc/29741/cdc_29741_DS1.pdf
• File Type:
  [PDF - 748.64 KB ]