Marine Fungal Communities: Metabolic Engineering for Secondary Metabolites and Their Industrial Applications

Author(s):  
Mohamad Hesam Shahrajabian ◽  
Ram B. Singh ◽  
Anathi Magadlela ◽  
Wenli Sun ◽  
Qi Cheng
2020 ◽  
Vol 8 (12) ◽  
pp. 1849
Author(s):  
Yujin Jeong ◽  
Sang-Hyeok Cho ◽  
Hookeun Lee ◽  
Hyung-Kyoon Choi ◽  
Dong-Myung Kim ◽  
...  

Cyanobacteria, given their ability to produce various secondary metabolites utilizing solar energy and carbon dioxide, are a potential platform for sustainable production of biochemicals. Until now, conventional metabolic engineering approaches have been applied to various cyanobacterial species for enhanced production of industrially valued compounds, including secondary metabolites and non-natural biochemicals. However, the shortage of understanding of cyanobacterial metabolic and regulatory networks for atmospheric carbon fixation to biochemical production and the lack of available engineering tools limit the potential of cyanobacteria for industrial applications. Recently, to overcome the limitations, synthetic biology tools and systems biology approaches such as genome-scale modeling based on diverse omics data have been applied to cyanobacteria. This review covers the synthetic and systems biology approaches for advanced metabolic engineering of cyanobacteria.


Catalysts ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 883 ◽  
Author(s):  
Young Chan Jeon ◽  
Anh Duc Nguyen ◽  
Eun Yeol Lee

Methane is a promising carbon feedstock for industrial biomanufacturing because of its low price and high abundance. Recent advances in metabolic engineering and systems biology in methanotrophs have made it possible to produce a variety of value-added compounds from methane, including secondary metabolites. Isoprenoids are one of the largest family of secondary metabolites and have many useful industrial applications. In this review, we highlight the current efforts invested to methanotrophs for the production of isoprenoids and other secondary metabolites, including riboflavin and ectoine. The future outlook for improving secondary metabolites production (especially of isoprenoids) using metabolic engineering of methanotrophs is also discussed.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Zhenyu Zhang ◽  
Pengfu Liu ◽  
Weike Su ◽  
Huawei Zhang ◽  
Wenqian Xu ◽  
...  

AbstractTrans-4-hydroxy-l-proline is an important amino acid that is widely used in medicinal and industrial applications, particularly as a valuable chiral building block for the organic synthesis of pharmaceuticals. Traditionally, trans-4-hydroxy-l-proline is produced by the acidic hydrolysis of collagen, but this process has serious drawbacks, such as low productivity, a complex process and heavy environmental pollution. Presently, trans-4-hydroxy-l-proline is mainly produced via fermentative production by microorganisms. Some recently published advances in metabolic engineering have been used to effectively construct microbial cell factories that have improved the trans-4-hydroxy-l-proline biosynthetic pathway. To probe the potential of microorganisms for trans-4-hydroxy-l-proline production, new strategies and tools must be proposed. In this review, we provide a comprehensive understanding of trans-4-hydroxy-l-proline, including its biosynthetic pathway, proline hydroxylases and production by metabolic engineering, with a focus on improving its production.


2019 ◽  
Author(s):  
Yingshuo Hou ◽  
Siyu Chen ◽  
Jianjun Wang ◽  
Guizhen Liu ◽  
Sheng Wu ◽  
...  

Abstract Background:Corynebacterium ammoniagenes is an important industrial organism that is widely used to produce nucleotides and the potential for industrial production of coenzyme A by Corynebacterium ammoniagenes ATCC 6871 has been shown. However, the yield of coenzyme A needs to be improved and the available constitutive promoters are rather limited in this strain. Results:In this study, 20 putative DNA promoters derived from genes with high transcription levels and 6 promoters from molecular chaperone genes were identified. To evaluate the activity of each promoter, red fluorescence protein (RFP) was used as a reporter. We successfully isolated a range of promoters with different activity levels resulting in different fluorescent intensities. A fragment derived from the upstream sequence of the 50S ribosomal protein L21 (Prpl21) exhibited the strongest activity among the 26 identified promoters. Furthermore, type III pantothenate kinase from Pseudomonas putida (PpcoaA) was overexpressed in C. ammoniagenes under the control of Prpl21, CoA yield increased approximately 4.1 times. Conclusions:This study provides a paradigm for rational isolation of promoters with different activities and their application in metabolic engineering. These promoters will enrich the available promoter toolkit for C. ammoniagenes and should be valuable in current platforms for metabolic engineering and synthetic biology for the optimization of pathways to extend the product spectrum or improve the productivity in C. ammoniagenes ATCC 6871 for industrial applications.


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.


2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Vijaydev Ganesan ◽  
Michael Spagnuolo ◽  
Ayushi Agrawal ◽  
Spencer Smith ◽  
Difeng Gao ◽  
...  

AbstractYarrowia lipolytica has emerged as a biomanufacturing platform for a variety of industrial applications. It has been demonstrated to be a robust cell factory for the production of renewable chemicals and enzymes for fuel, feed, oleochemical, nutraceutical and pharmaceutical applications. Metabolic engineering of this non-conventional yeast started through conventional molecular genetic engineering tools; however, recent advances in gene/genome editing systems, such as CRISPR–Cas9, transposons, and TALENs, has greatly expanded the applications of synthetic biology, metabolic engineering and functional genomics of Y. lipolytica. In this review we summarize the work to develop these tools and their demonstrated uses in engineering Y. lipolytica, discuss important subtleties and challenges to using these tools, and give our perspective on important gaps in gene/genome editing tools in Y. lipolytica.


2021 ◽  
Vol 16 (3) ◽  
Author(s):  
Asifa Mushtaq ◽  
Musharaf Gul ◽  
Seema Rawat ◽  
Jay Krishan Tiwari

Actinomycetes are prolific producers of secondary metabolites majority of which have phenomenal industrial applications. Actinomycetes recovered from cave habitats have generated a considerable interest among the scientific community with respect to their adaptability under such unique environmental conditions. Garhwal Himalaya, Uttarakhand abodes several pristine caves which have not been previously explored for the presence of actinomycetes. The present study has been undertaken to assess the in vitro antibacterial properties of actinomycetes recovered from some of the caves located in Garhwal Himalayan region. In the present study, a total of 127 actinomycetes were isolated from three distinct caves. Majority of the isolates exhibited antibacterial activity against gram-positive bacteria. Actinomycetes isolates RCM1 and SCMM1 were observed to evince promising antibacterial activities. Members of Streptomyces genus were found to be predominant in all the samples.


Author(s):  
Christoph Wawrosch ◽  
Sergey B. Zotchev

AbstractMedicinal plants have been used by mankind since ancient times, and many bioactive plant secondary metabolites are applied nowadays both directly as drugs, and as raw materials for semi-synthetic modifications. However, the structural complexity often thwarts cost-efficient chemical synthesis, and the usually low content in the native plant necessitates the processing of large amounts of field-cultivated raw material. The biotechnological manufacturing of such compounds offers a number of advantages like predictable, stable, and year-round sustainable production, scalability, and easier extraction and purification. Plant cell and tissue culture represents one possible alternative to the extraction of phytochemicals from plant material. Although a broad commercialization of such processes has not yet occurred, ongoing research indicates that plant in vitro systems such as cell suspension cultures, organ cultures, and transgenic hairy roots hold a promising potential as sources for bioactive compounds. Progress in the areas of biosynthetic pathway elucidation and genetic manipulation has expanded the possibilities to utilize plant metabolic engineering and heterologous production in microorganisms. This review aims to summarize recent advances in the in vitro production of high-value plant secondary metabolites of medicinal importance.Key points• Bioactive plant secondary metabolites are important for current and future use in medicine• In vitro production is a sustainable alternative to extraction from plants or costly chemical synthesis• Current research addresses plant cell and tissue culture, metabolic engineering, and heterologous production Graphical abstract


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