scholarly journals HEx: A heterologous expression platform for the discovery of fungal natural products

2018 ◽  
Vol 4 (4) ◽  
pp. eaar5459 ◽  
Author(s):  
Colin J. B. Harvey ◽  
Mancheng Tang ◽  
Ulrich Schlecht ◽  
Joe Horecka ◽  
Curt R. Fischer ◽  
...  
Keyword(s):  
Natural Products ◽  
Heterologous Expression ◽  
Expression Platform ◽  
Fungal Natural Products

scholarly journals HEx: a heterologous expression platform for the discovery of fungal natural products

2018 ◽  
Author(s):  
Colin JB Harvey ◽  
Mancheng Tang ◽  
Ulrich Schlecht ◽  
Joe Horecka ◽  
Curt R Fischer ◽  
...  
Keyword(s):  
Natural Products ◽  
Synthetic Biology ◽  
Heterologous Expression ◽  
Gene Clusters ◽  
Fungal Species ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Expression Platform ◽  
The World ◽  
Fungal Natural Products

AbstractFor decades, fungi have been a source of FDA-approved natural products such as penicillin, cyclosporine, and the statins. Recent breakthroughs in DNA sequencing suggest that millions of fungal species exist on Earth with each genome encoding pathways capable of generating as many as dozens of natural products. However, the majority of encoded molecules are difficult or impossible to access because the organisms are uncultivable or the genes are transcriptionally silent. To overcome this bottleneck in natural product discovery, we developed the HEx (Heterologous EXpression) synthetic biology platform for rapid, scalable expression of fungal biosynthetic genes and their encoded metabolites in Saccharomyces cerevisiae. We applied this platform to 41 fungal biosynthetic gene clusters from diverse fungal species from around the world, 22 of which produced detectable compounds. These included novel compounds with unexpected biosynthetic origins, particularly from poorly studied species. This result establishes the HEx platform for rapid discovery of natural products from any fungal species, even those that are uncultivable, and opens the door to discovery of the next generation of natural products.SummaryHere we present the largest scale effort reported to date toward the complete refactoring and heterologous expression of fungal biosynthetic gene clusters utilizing HEx, a novel synthetic biology platform.

Fungal natural products targeting chronic lymphocytic leukemia

Planta Medica ◽  
2012 ◽  
Vol 78 (11) ◽  
Author(s):  
T Thorskov Bladt ◽  
S Kildgaard ◽  
P Boldsen Knudsen ◽  
C Held Gotfredsen ◽  
C Dürr ◽  
...  
Keyword(s):  
Natural Products ◽  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Fungal Natural Products

scholarly journals Core Steps to the Azaphilone Family of Fungal Natural Products

ChemBioChem ◽  
2021 ◽  
Author(s):  
Katherine Williams ◽  
Claudio Greco ◽  
Andrew M. Bailey ◽  
Christine L. Willis
Keyword(s):  
Natural Products ◽  
Fungal Natural Products

scholarly journals MeFSAT: a curated natural product database specific to secondary metabolites of medicinal fungi

RSC Advances ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 2596-2607
Author(s):  
R. P. Vivek-Ananth ◽  
Ajaya Kumar Sahoo ◽  
Kavyaa Kumaravel ◽  
Karthikeyan Mohanraj ◽  
Areejit Samal
Keyword(s):  
Natural Products ◽  
Secondary Metabolites ◽  
Natural Product ◽  
Chemical Space ◽  
Therapeutic Uses ◽  
Medicinal Fungi ◽  
Fungal Natural Products

First dedicated manually curated resource on secondary metabolites and therapeutic uses of medicinal fungi. Cheminformatics based analysis of the chemical space of fungal natural products.

scholarly journals Discovery and Biosynthesis of Natural Products from New Zealand Soil Metagenome Libraries

2021 ◽  
Author(s):  
◽  
Luke Stevenson
Keyword(s):  
Natural Products ◽  
New Zealand ◽  
Heterologous Expression ◽  
Gene Clusters ◽  
Bioinformatic Analysis ◽  
Coli Strain ◽  
Functional Screening ◽  
Functional Difference ◽  
Biosynthetic Pathways ◽  
New Members

<p>Antibiotic discovery rates dramatically declined following the “golden age” of the 1940’s to the 1960’s. The platforms that underpinned that age of discovery rested upon laboratory cultivation of a small clade of bacteria, the actinomycetes, primarily isolated from soil environments. Fermentation extracts of these isolated bacteria have provided the majority of antibiotics and anticancer small molecules still used today. By applying modern genetic analysis techniques to these same environmental sources that have previously yielded such success, we can uncover new biosynthetic pathways, and bioactive compounds. The work described in this thesis investigated New Zealand soil metagenomes for this purpose.  Four large metagenome libraries were constructed from the microbiomes of diverse soil environments. These were then interrogated by a functional screening approach in a knockout Escherichia coli strain, to recover a large collection of the biosynthetic gene clusters responsible for bacterial secondary metabolite production. Using different modes of bioinformatic analysis, these gene clusters were demonstrated to have both phylogenetic divergence, and functional difference from bacterial biosynthesis pathways previously discovered from culture based studies.  Two additional biosynthetic pathways were recovered from one of these metagenome libraries, and in each case found to have novel genetic features. These gene clusters were further studied by heterologous expression within Streptomyces albus production hosts. One of these gene clusters produced small aromatic polyketide compounds, the structure of one of which was solved by chemical analytic techniques, and found to be a new chemical entity.  The second gene cluster was demonstrated to have similarity to known aureolic acid biosynthesis gene clusters – a class of potent anticancer natural products. Heterologous expression resulted in the production of many metabolites, two of which were characterised and found to be new members of this chemical class.  The research in this thesis both validates the use of metagenomic analysis for future natural product discovery efforts, and adds to a growing body of evidence that understudied clades of bacteria have an untapped biosynthetic potential that can be accessed by metagenomic methods.</p>

scholarly journals Expanding the Natural Products Heterologous Expression Repertoire in the Model Cyanobacterium Anabaena sp. Strain PCC 7120: Production of Pendolmycin and Teleocidin B-4

2019 ◽  
Vol 9 (1) ◽  
pp. 63-75 ◽  
Author(s):  
Patrick Videau ◽  
Kaitlyn N. Wells ◽  
Arun J. Singh ◽  
Jessie Eiting ◽  
Philip J. Proteau ◽  
...  
Keyword(s):  
Natural Products ◽  
Heterologous Expression ◽  
Cyanobacterium Anabaena ◽  
Anabaena Sp ◽  
Pcc 7120

Fungal natural products in research and development

2014 ◽  
Vol 31 (10) ◽  
pp. 1425-1448 ◽  
Author(s):  
Anja Schueffler ◽  
Timm Anke
Keyword(s):  
Natural Products ◽  
Research And Development ◽  
Fungal Natural Products
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