Genome Mining of Oxidation Modules in trans‐Acyltransferase Polyketide Synthases Reveals a Culturable Source for Lobatamides

Abstract

+ ] These authors contributed equally to this work.Supporting information (including experimental details) and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

Mining and unearthing hidden biosynthetic potential

“…Comparative screening of culture extracts of a deletion mutant and the wild-type strain uncovered novel polyketides with rare epoxide and cyclopropyl moieties 53 . Similarly, mining for genes encoding oxygenase-containing modules in trans-AT PKS systems led to the discovery of the BGC for lobatamide A (12) in the culturable plant symbiont Gynuella sunshinyii 54 .…”

Discovery of new enzymatic functions and metabolic pathways using genomic enzymology web tools

“…For RODEO, user-supplied lists of enzymes involved in the syntheses of ribosomally synthesized and post-translationally modified peptides (RiPPs) are used as input; the retrieved genome neighborhoods are mined for short precursor peptides that often are not identified in genome annotation. EFI-EST and EFI-GNT have been used to identify genome neighborhoods that contain orthologues/homologues of key enzymes in natural product biosynthesis, e.g., thioamide synthases [38], enzymes involved in diazeniumdiolate siderophore synthesis [39], enzymes in endopyrrole biosynthesis [40], enzymes in polytheonamide biosynthesis [41], and flavoprotein monooxygenases (Baeyer-Villiger-type oxygen insertion) in polyketide synthase natural products [42]. In some cases, Option A of EFI-EST (BLAST using a user-specified query) is used to generate the SSN of homologues/orthologues in the UniProt database; EFI-GNT is used to visualize/analyze the BGCs.…”

Highlights of marine natural products having parallel scaffolds found from marine-derived bacteria, sponges, and tunicates

“…Over two decades later, genome mining focused on identifying the products of diverse oxidation and directed researchers to focus on the polyketide synthases-associated flavoprotein monooxygenases involved in the biosynthesis of oxygen containing polyketides. The biosynthetic modules identified from the plant-derived Proteobacteria, Gynuella sunshinyii [157], were identified as responsible for the oxygen incorporation in the biosynthesis of 91, and also provided a biosynthetic hypothesis for insertion of oxygen atoms into the macrocyclic cores of sponge-derived salarin A and pateamine A (65). A 5 L culture provided an unspecified amount of 91 that was rigorously characterized by NMR and MS.…”