A single amino acid residue controls acyltransferase activity in a polyketide synthase from Toxoplasma gondii .

Journal Article (Journal Article)

Type I polyketide synthases (PKSs) are multidomain, multimodule enzymes capable of producing complex polyketide metabolites. These modules contain an acyltransferase (AT) domain, which selects acyl-CoA substrates to be incorporated into the metabolite scaffold. Herein, we reveal the sequences of three AT domains from a polyketide synthase (Tg PKS2) from the apicomplexan parasite Toxoplasma gondii . Phylogenic analysis indicates these ATs (AT1, AT2, and AT3) are distinct from domains in well-characterized microbial biosynthetic gene clusters. Biochemical investigations revealed that AT1 and AT2 hydrolyze malonyl-CoA but the terminal AT3 domain is non-functional. We further identify an "on-off switch" residue that controls activity such that a single amino acid change in AT3 confers hydrolysis activity while the analogous mutation in AT2 eliminates activity. This biochemical analysis of AT domains from an apicomplexan PKS lays the foundation for further molecular and structural studies on PKSs from T. gondii and other protists.

Full Text

Duke Authors

Cited Authors

  • D'Ambrosio, HK; Ganley, JG; Keeler, AM; Derbyshire, ER

Published Date

  • June 2022

Published In

Volume / Issue

  • 25 / 6

Start / End Page

  • 104443 -

PubMed ID

  • 35874921

Pubmed Central ID

  • PMC9301873

Electronic International Standard Serial Number (EISSN)

  • 2589-0042

International Standard Serial Number (ISSN)

  • 2589-0042

Digital Object Identifier (DOI)

  • 10.1016/j.isci.2022.104443


  • eng