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Generating polyketide diversity in Dictyostelium: a Steely hybrid polyketide synthase produces alternate products at different developmental stages.

Published version
Peer-reviewed

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Authors

Iijima, Tomoyuki 
Koyama, Kohei 
Shinagawa, Tomonori 
Yamanaka, Ayaka 

Abstract

The soil is a rich ecosystem where many ecological interactions are mediated by small molecules, and in which amoebae are low-level predators and also prey. The social amoeba Dictyostelium discoideum has a high genomic potential for producing polyketides to mediate its ecological interactions, including the unique 'Steely' enzymes, consisting of a fusion between a fatty acid synthase and a chalcone synthase. We report here that D. discoideum further increases its polyketide potential by using the StlB Steely enzyme, and a downstream chlorinating enzyme, to make both a chlorinated signal molecule, DIF-1, during its multi-cellular development, and a set of abundant polyketides in terminally differentiated stalk cells. We identify one of these as a chlorinated dibenzofuran with potent anti-bacterial activity. To do this, StlB switches expression from prespore to stalk cells in late development and is cleaved to release the chalcone synthase domain. Expression of this domain alone in StlB null cells allows synthesis of the stalk-associated, chlorinated polyketides. Thus, by altered expression and processing of StlB, cells make first a signal molecule, and then abundant secondary metabolites, which we speculate help to protect the mature spores from bacterial infection.

Description

Peer reviewed: True

Keywords

Development and physiology, Research articles, Dictyostelium discoideum, polyketide synthase, dibenzofuran, differentiation-inducing factor (DIF), antibacterial compound

Journal Title

Proc Biol Sci

Conference Name

Journal ISSN

0962-8452
1471-2954

Volume Title

Publisher

The Royal Society
Sponsorship
Japan Society for the Promotion of Science (19K05850, 15K01807)
the Medical Research Council (part of UK Research and Innovation) (MRC file reference number MC_U105178783)