1887

Abstract

Nature serves as a rich source of molecules with immense chemical diversity. Aptly named, these ‘natural products’ boast a wide variety of environmental, medicinal and industrial applications. Type II polyketides, in particular, confer substantial medicinal benefits, including antibacterial, antifungal, anticancer and anti-inflammatory properties. These molecules are produced by enzyme assemblies known as type II polyketide synthases (PKSs), which use domains such as the ketosynthase chain-length factor and acyl carrier protein to produce polyketides with varying lengths, cyclization patterns and oxidation states. In this work, we use a novel bioinformatic workflow to identify biosynthetic gene clusters (BGCs) that code for the core type II PKS enzymes. This method does not rely on annotation and thus was able to unearth previously ‘hidden’ type II PKS BGCs. This work led us to identify over 6000 putative type II PKS BGCs spanning a diverse set of microbial phyla, nearly double those found in most recent studies. Notably, many of these newly identified BGCs were found in non-actinobacteria, which are relatively underexplored as sources of type II polyketides. Results from this work lay an important foundation for future bioprospecting and engineering efforts that will enable sustainable access to diverse and structurally complex molecules with medicinally relevant properties.

Funding
This study was supported by the:
  • Barry Goldwater Scholarship
    • Principle Award Recipient: ChristinaM. McBride
  • Arnold and Mabel Beckman Foundation
    • Principle Award Recipient: ChristinaM. McBride
  • National Science Foundation (Award CHE2201984)
    • Principle Award Recipient: LouiseK. Charkoudian
  • National Science Foundation (Award CHE1652424)
    • Principle Award Recipient: LouiseK. Charkoudian
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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/content/journal/mgen/10.1099/mgen.0.000965
2023-03-23
2024-06-20
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