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Heterologous production of biomedically relevant fungal metabolites in Aspergillus nidulans

Heck, Quinn Kalby (2020) MOBN03 20201
Degree Projects in Molecular Biology
Popular Abstract
Genetic engineering of molds to produce new pharmaceutical compounds

In this master’s thesis project, I investigated natural chemicals produced by fungi which are interesting for the pharmaceutical industry. Fungi are a very large family of organisms that we are still working to understand, and we continue to discover many new species every year. Living by growing on food sources and secreting enzymes to break them down, fungi then engulf the broken-down food. In their lifecycle which is almost entirely at the microscopic level, they interact with diverse environments including other microscopic organisms, and have evolved to produce a wide variety of chemical compounds which they use to interact with their environments. These include... (More)
Genetic engineering of molds to produce new pharmaceutical compounds

In this master’s thesis project, I investigated natural chemicals produced by fungi which are interesting for the pharmaceutical industry. Fungi are a very large family of organisms that we are still working to understand, and we continue to discover many new species every year. Living by growing on food sources and secreting enzymes to break them down, fungi then engulf the broken-down food. In their lifecycle which is almost entirely at the microscopic level, they interact with diverse environments including other microscopic organisms, and have evolved to produce a wide variety of chemical compounds which they use to interact with their environments. These include defensive compounds that allow them to fight off other species of fungi and bacteria, such as penicillin.

For this project I worked with the filamentous fungi Aspergillus nidulans to produce natural products which have potential uses to the biomedical industry. I did this through genetic engineering with CRISPR-cas9, a sort of DNA scissors which makes genetic engineering much easier. I also used a method, which is new to filamentous fungi, where pieces of DNA are designed to self-assemble for genetic engineering called in vivo assembly. By using self-assembling pieces of DNA, I did not have to do time intensive plasmid cloning, saving a great deal of time that is normally needed to insert many genes. In my project I worked to insert artificial gene clusters in A. nidulans to produce specific fungal compounds.

I focused on two gene clusters in my project, the first being the psilocybin gene cluster, from two species Psilocybe cubensis and Gymnopilus dilepis, and the second an ergot alkaloid gene cluster from Aspergillus homomorphus. Both of which are biomedically interesting as recent medical research has found them to have a high potential for treating a wide variety of mental health disorders such as depression, anxiety, and addiction.

In my project I showed that it is feasible, using in vivo assembly to recreate large gene clusters in molds. And these artificially created strains were able to produce compounds of interest from the gene cluster. Which creates a solid foundation for future research and possible opportunities to produce larger amounts of valuable compounds.

In the pictures to the right one of my strains which produces a large amount of red chemicals can be seen. In the top photo the mold growing on an agar plate can be seen, and in the bottom photo the mold clearly secretes the red compound into the gel. This strain was not a pharmaceutically interesting strain, but it shows the potential in using fungi as cellular factories for production of chemicals.


Master’s Degree Project in Molecular Biology 60 credits 2020
Department of Biology, Lund University

Advisor: Jakob Blæsbjerg Hoof
Advisor’s institution: Denmark’s Technical University (DTU), Department of bioengineering (Less)
Please use this url to cite or link to this publication:
author
Heck, Quinn Kalby
supervisor
organization
course
MOBN03 20201
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
9039033
date added to LUP
2021-02-01 16:10:32
date last changed
2021-02-01 16:10:32
@misc{9039033,
  author       = {{Heck, Quinn Kalby}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Heterologous production of biomedically relevant fungal metabolites in Aspergillus nidulans}},
  year         = {{2020}},
}