Development of synthetic biology tools for accelerating fungal natural product discovery

Indra Roux

doi:10.26182/sbvv-v071

Development of synthetic biology tools for accelerating fungal natural product discovery

Indra Roux

Research output: Thesis › Doctoral Thesis

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Abstract

Filamentous fungi are a major source of secondary metabolites with biotechnological applications. The aim of this thesis is to develop synthetic biology tools to accelerate the discovery of fungal compounds. First, a system of artificial transcription factors based on CRISPR/Cas (CRISPRa) was developed to activate the expression of silent biosynthetic pathways. Second, a system for targeted chromosomal integration of large biosynthetic gene clusters using site-specific recombinases was developed. Additionally, the biosynthesis of the polyketide burnettiene A was investigated by heterologous expression in Aspergillus nidulans. The tools developed in this thesis represent a valuable expansion to the filamentous fungi synthetic biology toolbox.

Original language	English
Qualification	Doctor of Philosophy
Awarding Institution	The University of Western Australia
Supervisors/Advisors	Chooi, Heng, Supervisor Mylne, Josh, Supervisor Waters, Mark, Supervisor
Award date	20 May 2021
DOIs	https://doi.org/10.26182/sbvv-v071
Publication status	Unpublished - 2021

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Embargoed from 30/05/2021 to 30/08/2021. Made publicly available on 30/08/2021.

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10.26182/sbvv-v071

THESIS - DOCTOR OF PHILOSOPHY - ROUX, Indra - 2021 - Pt. 1
THESIS - DOCTOR OF PHILOSOPHY - ROUX, Indra - 2021 - Pt. 2
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Cite this

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title = "Development of synthetic biology tools for accelerating fungal natural product discovery",

abstract = "Filamentous fungi are a major source of secondary metabolites with biotechnological applications. The aim of this thesis is to develop synthetic biology tools to accelerate the discovery of fungal compounds. First, a system of artificial transcription factors based on CRISPR/Cas (CRISPRa) was developed to activate the expression of silent biosynthetic pathways. Second, a system for targeted chromosomal integration of large biosynthetic gene clusters using site-specific recombinases was developed. Additionally, the biosynthesis of the polyketide burnettiene A was investigated by heterologous expression in Aspergillus nidulans. The tools developed in this thesis represent a valuable expansion to the filamentous fungi synthetic biology toolbox.",

keywords = "filamentous fungi, Synthetic Biology, secondary metabolites, CRISPRa, recombinases, Heterologous expression, Aspergillus nidulans, Polyketide",

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AB - Filamentous fungi are a major source of secondary metabolites with biotechnological applications. The aim of this thesis is to develop synthetic biology tools to accelerate the discovery of fungal compounds. First, a system of artificial transcription factors based on CRISPR/Cas (CRISPRa) was developed to activate the expression of silent biosynthetic pathways. Second, a system for targeted chromosomal integration of large biosynthetic gene clusters using site-specific recombinases was developed. Additionally, the biosynthesis of the polyketide burnettiene A was investigated by heterologous expression in Aspergillus nidulans. The tools developed in this thesis represent a valuable expansion to the filamentous fungi synthetic biology toolbox.

KW - filamentous fungi

KW - Synthetic Biology

KW - secondary metabolites

KW - CRISPRa

KW - recombinases

KW - Heterologous expression

KW - Aspergillus nidulans

KW - Polyketide

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DO - 10.26182/sbvv-v071

M3 - Doctoral Thesis

ER -

Development of synthetic biology tools for accelerating fungal natural product discovery

Abstract

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