Strain Improvement for the Production of Fungal Secondary Metabolites

Author(s):  
Prakash Masurekar
2021 ◽  
Author(s):  
Guokun Wang ◽  
Douglas B. Kell ◽  
Irina Borodina

Abstract Fungal secondary metabolites (FSMs) represent a remarkable array of bioactive compounds, with potential applications as pharmaceuticals, nutraceuticals, and agrochemicals. However, these molecules are typically produced only in limited amounts by their native hosts. The native organisms may also be difficult to cultivate and genetically engineer, and some can produce undesirable toxic side-products. Alternatively, recombinant production of fungal bioactives can be engineered into industrial cell factories, such as aspergilli or yeasts, which are well amenable for large-scale manufacturing in submerged fermentations. In this review, we summarize the development of baker’s yeast Saccharomyces cerevisiae to produce compounds derived from filamentous fungi and mushrooms. These compounds mainly include polyketides, terpenoids, and amino acid derivatives. We also describe how native biosynthetic pathways can be combined or expanded to produce novel derivatives and new-to-nature compounds. We describe some new approaches for cell factory engineering, such as genome-scale engineering, biosensor-based high-throughput screening, and machine learning, and how these tools have been applied for S. cerevisiae strain improvement. Finally, we prospect the challenges and solutions in further development of yeast cell factories to more efficiently produce FSMs.


Fungi ◽  
2018 ◽  
pp. 318-371
Author(s):  
P.M. Cano ◽  
O. Puel ◽  
I.P. Oswald

2021 ◽  
Vol 13 (3) ◽  
pp. 11020
Author(s):  
Peter M. EZE ◽  
Ying GAO ◽  
Yang LIU ◽  
Lasse Van GEELEN ◽  
Chika P. EJIKEUGWU ◽  
...  

Extremophilic fungi have received considerable attention recently as new promising sources of biologically active compounds with potential pharmaceutical applications. This study investigated the secondary metabolites of a marine-derived Penicillium ochrochloron isolated from underwater sea sand collected from the North Sea in St. Peter-Ording, Germany. Standard techniques were used for fungal isolation, taxonomic identification, fermentation, extraction, and isolation of fungal secondary metabolites. Chromatographic separation and spectroscopic analyses of the fungal secondary metabolites yielded eight compounds: talumarin A (1), aspergillumarin A (2), andrastin A (3), clavatol (4), 3-acetylphenol (5), methyl 2,5-dihydro-4-hydroxy-5-oxo-3-phenyl-2-furanpropanoate (6), emodin (7) and 2-chloroemodin (8). After co-cultivation with Bacillus subtilis, the fungus was induced to express (-)-striatisporolide A (9). Compound 1 was evaluated for antibacterial activity against Staphylococcus aureus, Acinetobacter baumannii, Mycobacterium smegmatis, and M. tuberculosis, as well as cytotoxicity against THP-1 cells. The compound, however, was not cytotoxic to THP-1 cells and had no antibacterial activity against the microorganisms tested. The compounds isolated from P. ochrochloron in this study are well-known compounds with a wide range of beneficial biological properties that can be explored for pharmaceutical, agricultural, or industrial applications. This study highlights the bioprospecting potential of marine fungi and confirms co-cultivation as a useful strategy for the discovery of new natural products.


2009 ◽  
Vol 72 (9) ◽  
pp. 2006-2016 ◽  
Author(s):  
BULENT KABAK ◽  
ALAN D. W. DOBSON

Mycotoxins are fungal secondary metabolites that if ingested can cause a variety of adverse effects on both humans and animals, ranging from allergic responses to death. Therefore, exposure to mycotoxins should be minimized. A variety of physical, chemical, and biological methods have been developed for decontamination and/or detoxification of mycotoxins from contaminated foods and feeds. This overview details the latest developments in the biological control of both fungal infection and mycotoxin formation and describes the detoxification of many of the most important mycotoxins by microorganisms. This review also addresses the potential for use of microorganisms as mycotoxin binders in the gastrointestinal tract of both humans and animals, thereby reducing the potential deleterious effects of exposure to these toxins.


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