Title : Modular Halogenation, alpha-Hydroxylation, and Acylation by a Remarkably Versatile Polyketide Synthase - Hemmerling_2022_Angew.Chem.Int.Ed.Engl__e202116614 |
Author(s) : Hemmerling F , Meoded RA , Fraley AE , Minas HA , Dieterich CL , Rust M , Ueoka R , Jensen K , Helfrich EJN , Bergande C , Biedermann M , Magnus N , Piechulla B , Piel J |
Ref : Angew Chem Int Ed Engl , :e202116614 , 2022 |
Abstract :
Bacterial multimodular polyketide synthases (PKSs) are large enzymatic assembly lines that synthesize many bioactive natural products of therapeutic relevance. While PKS catalysis is mostly based on fatty acid biosynthetic principles, polyketides can be further diversified by post-PKS enzymes. Here, we characterized a remarkably versatile trans-acyltransferase (trans-AT) PKS from Serratia that builds structurally complex macrolides via more than ten functionally distinct PKS modules. In the oocydin PKS, we identified a new oxygenation module that alpha-hydroxylates polyketide intermediates, a halogenating module catalyzing backbone gamma-chlorination, and modular O-acetylation by a thioesterase-like domain. These results from a single biosynthetic assembly line highlight the expansive biochemical repertoire of trans-AT PKSs and provide diverse modular tools for engineered biosynthesis from a close relative of E.coli. |
PubMedSearch : Hemmerling_2022_Angew.Chem.Int.Ed.Engl__e202116614 |
PubMedID: 35020279 |
Gene_locus related to this paper: serpl-k7wyz4 |
Gene_locus | serpl-k7wyz4 |
Hemmerling F, Meoded RA, Fraley AE, Minas HA, Dieterich CL, Rust M, Ueoka R, Jensen K, Helfrich EJN, Bergande C, Biedermann M, Magnus N, Piechulla B, Piel J (2022)
Modular Halogenation, alpha-Hydroxylation, and Acylation by a Remarkably Versatile Polyketide Synthase
Angew Chem Int Ed Engl
:e202116614
Hemmerling F, Meoded RA, Fraley AE, Minas HA, Dieterich CL, Rust M, Ueoka R, Jensen K, Helfrich EJN, Bergande C, Biedermann M, Magnus N, Piechulla B, Piel J (2022)
Angew Chem Int Ed Engl
:e202116614