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Expanding the structural diversity of polyketides by exploring the cofactor tolerance of an inline methyltransferase domain.

ABSTRACT: 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-? pyrone or be processed fully into the alkyne-containing 4'-propargyl-chaetoviridin A.

SUBMITTER: Winter JM

PROVIDER: S-EPMC3779521 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Expanding the structural diversity of polyketides by exploring the cofactor tolerance of an inline methyltransferase domain.

Winter Jaclyn M JM Chiou Grace G Bothwell Ian R IR Xu Wei W Garg Neil K NK Luo Minkui M Tang Yi Y

Organic letters 20130709 14

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 ...[more]

PMID: 23837609

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