A Baltic Sea microbiome-derived Type III polyketide synthase produces host-protective alkylresorcinols in E. coli
Susana López-Gutiérrez, Laura A. Espinosa-Barrera, Arianna Soto-Hernández, Holber Zuleta-Prada, Celia Bustos-Brito, César S. Cardona-Félix et al.
Publisher abstract excerptMarine microorganisms are a prolific source of novel polyketide synthases (PKSs) that generate structurally diverse and functional polyketides. Here, we identify a novel type III PKS, ArsMB, from Pontimonas sp. via metagenomic mining of a Baltic Sea microbiome. Heterologous expression of arsMB synth…
Abstract & author credits for A Baltic Sea microbiome-derived Type III polyketide synthase produces host-protective alkylresorcinols in E. coli
Authors: Susana López-Gutiérrez, Laura A. Espinosa-Barrera, Arianna Soto-Hernández, Holber Zuleta-Prada, Celia Bustos-Brito, César S. Cardona-Félix, José Utrilla, Beatriz Velazquez-Cruz, Yair Cárdenas-Conejo, Jesus Alfredo Araujo-León, Victor Aguilar-Hernández, Juan A. Osuna-Castro, Baldomero Esquivel, Hugo Serrano-Posada, Sara Centeno-Leija
Marine microorganisms are a prolific source of novel polyketide synthases (PKSs) that generate structurally diverse and functional polyketides. Here, we identify a novel type III PKS, ArsMB, from Pontimonas sp. via metagenomic mining of a Baltic Sea microbiome. Heterologous expression of arsMB synthetic gene in an Escherichia coli host that lacks a native type III PKS, combined with a two-step strategy to boost acyl-CoA precursor availability in a glucose-mineral medium, enabled the in vivo synthesis of two cell-associated alkylresorcinols, identified by GC-MS as 5-pentadecyl-1,3-benzenediol (ars1) and 5-tridecyl-1,3-benzenediol (ars2). The product profile is consistent with a tetraketide alkylresorcinol biosynthetic pathway utilizing C16 and C14 acyl starter units, drawn from the host acyl-CoA pool. In agreement, AlphaFold2-based structural modeling predicts a Cys139/His275/Asn308 catalytic triad and a long hydrophobic substrate tunnel compatible with long-chain acyl starter units. E. coli producing the amphipathic cell-associated alkylresorcinols ars1/ars2 exhibited increased resistance to muralytic digestion by endolysins and to hydrogen peroxide. These findings expand the known repertoire of marine-derived type III PKSs and highlight the biotechnological potential of ArsMB-derived alkylresorcinols.
Source: PLOS ONE. DOI: 10.1371/journal.pone.0361965. Abstract from the publisher’s feed; HTML formatting and repeated author line removed.