Yellow pigment keeps social amoebae together

Natural product controls multicellularity

Spherical structures of yellowish colour on long, thin stems
Microscopic image of the fruiting bodies of D. discoideum on an agar plate. The yellow pigment is visible at the tip of the multicellular organism, where the dormant spores are also located. Source: Rosa Herbst/Leibniz-HKI

The multicellular stage of the amoeba Dictyostelium discoideum is partially regulated by an intensely yellow natural product, as researchers of the Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute (Leibniz-HKI) have discovered. The newly identified natural substance of the polyketide family prevents the amoebae spores from hatching too early. The study was published in the scientific journal PNAS.

Social amoebae are unicellular organisms that can join together to form a multicellular organism visible to the naked eye when food is scarce. In a complex process, they form a fruiting body filled with spores that are carried on by wind or by animals.

"You can imagine this fruiting body like a water balloon," explains Rosa Herbst from the Department of Paleobiotechnology at the Leibniz-HKI, co-first author of the study. "It can easily burst and the spores are released."

In the current study, the researchers were able to identify a natural substance - a polyketide - that prevents the amoebae from hatching too early from the spores in the fruiting body, and thus significantly maintains the multicellular development cycle. The molecule has an intense yellow colour and is mainly found surrounding the spores in the fruiting body.

"Amoebae produce a variety of natural substances that could be interesting, for example, for the development of new medicines," explains Pierre Stallforth, head of the Department of Paleobiotechnology and professor at Friedrich Schiller University in Jena. He led the study together with Falk Hillmann, head of the research group Evolution of Microbial Interactions at Leibniz-HKI and now professor at Wismar University of Applied Sciences. In most cases, however, it is not known what the actual biological function of these substances is. The amoeba D. discoideum has 40 polyketide biosynthesis genes that code for enzymes that produce the polyketides.

Amoebae gather together to form a fruiting body. Some cells produce the yellow pigment (here fluorescing red) and die after the end of the multicellular phase. Source: Markus Günther/Leibniz-HKI

"Polyketide synthase 5, which we studied, is only the third one where we have an idea of the function and structure of the corresponding polyketide," points out Christin Reimer, co-first author. This is despite the fact that D. discoideum is an intensively researched model organism that is widely distributed in the soil.

The team, which involved several research groups at the Leibniz-HKI, combined data from transcriptome and metabolome analyses for the study. First, the researchers investigated which enzymes are produced during the formation of the fruiting body and selected the most promising one for further investigation. They switched off the corresponding gene with the help of the CRISPR-Cas9 gene scissors. By comparing it to the metabolites of the unmodified amoebae, they were able to identify the polyketide dictyoden, a yellow pigment.

Schematic representation of the developmental cycle of D. discoideum. As unicellular organisms, amoebae feed on bacteria. However, once this food source is exhausted, the cells begin to flock together to form a multicellular organism. About 24 hours later, a fruiting body has formed, which carries a "yellow balloon" of spores at its tip. If the spores are carried - for example by an insect - to a new location with a richer food supply, they hatch and the cycle begins again. Source: Markus Günther/Leibniz-HKI

"At first, we had no idea what this polyketide does," says third first author Markus Günther. However, the team found that in the amoebae without polyketide synthase 5, the fruiting bodies often contained amoebae that hatched too early. In further experiments, in which they reintroduced dictyodes, they were able to reverse this early hatching by 50 percent. "So obviously other substances play a role, but we assume that dictyoden is particularly important in suppressing early hatching."

"With this study, we have developed a reliable approach to study polyketides in their physiological and ecological context," says Pierre Stallforth. In further steps, the team also wants to explore other polyketide synthases of the amoeba and thus find out more about the complex transition from single- to multicellularity.

The research work of the Department of Paleobiotechnology is supported by the Leibniz Association and the Werner Siemens Foundation. The study was also funded by the Deutsche Forschungsgemeinschaft (German Research Foundation), among others within the framework of the Balance of the Microverse Cluster of Excellence and the ChemBioSys Collaborative Research Centre, by the European Social Fund, the European Regional Development Fund and the Federal Ministry of Education and Research.

Original publication

Günther M, Reimer C, Herbst R, Kufs JE, Rautschek J, Ueberschaar N, Zhang S, Peschel G, Reimer L, Regestein L, Valiante V, Hillmann F, Stallforth P (2022). Yellow polyketide pigment suppresses premature hatching in social amoeba. PNAS, doi: 10.1073/pnas.2116122119


Markus Günther
Rosa Herbst
Falk Hillmann
Johann Kufs
Gundela Peschel
Julia Rautschek
Lars Regestein
Christin Reimer
Lisa Reimer
Pierre Stallforth
Nico Ueberschaar
Vito Valiante
Shuaibing Zhang

Science communication & accreditation

Friederike Gawlik
Charlotte Fuchs


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