scholarly journals Random Mutagenesis of Filamentous Fungi Strains for High-Yield Production of Secondary Metabolites: The Role of Polyamines

2020 ◽  
Author(s):  
Alexander A. Zhgun

A filamentous fungus (also called molds or moldy fungus) is a taxonomically diverse organism from phylum Zygomycota and Ascomycota with filamentous hyphae and has the ability to produce airborne spores or conidia. Currently, more than 70,000 molds are known, and some of them contain unique and unusual biochemical pathways. A number of products from such pathways, especially, the secondary metabolite (SM) pathways are used as important pharmaceuticals, including antibiotics, statins, and immunodepresants. Under different conditions, the individual species can produce more than 100 SM. The strain improvement programs lead to high yielding in target SM and significant reduction of spin-off products. The main tool for the strain improvement of filamentous fungi is random mutagenesis and screening. The majority of industrial overproducing SM strains were developed with the help of such technique over the past 50–70 years; the yield of the target SM increased by 100- to 1000-fold or more. Moreover, most of the strains have reached their technological limit of improvement. A new round of mutagenesis has not increased overproduction. Recently, it was shown that that the addition of exogenous polyamines may increase the production of such improved strains of filamentous fungi. The possible molecular mechanism of this phenomenon and its biotechnological applications are discussed.

2020 ◽  
Author(s):  
Chenyang Wang ◽  
Junjun Wu ◽  
Lei Wang ◽  
Xiaojia Chen ◽  
Qinyu Li ◽  
...  

Abstract Background: L-serine is widely used in the food, cosmetic and pharmaceutical industries, and direct fermentation of L-serine from glucose is an attractive technique. However, L-serine producers have historically been developed via classical random mutagenesis due to the complicated metabolic network and regulatory mechanism of L-serine production, leading to un-optimal productivity and yield of L-serine and thus limiting its large-scale industrial production. Result: In this study, a high-yield and high-productivity Escherichia coli strain was constructed by a defined genetic modification methodology for L-serine production. First, L-serine-mediated feedback inhibition was removed and L-serine biosynthetic pathway genes (serAfr, serC and serB) associated with phosphoglycerate kinase (pgk) were overexpressed. Secondly, L-serine conversion pathway was further examined by introducing a glyA mutation (K229G) and deleting other degrading enzymes based on deletion of initial sdaA. Finally, the L-serine transport system was rationally engineered to reduce the uptake and accelerate the export of L-serine. The optimally engineered strain produced 35 g/L L-serine with a productivity of 0.98 g/L/h and yield of 0.42 g/g glucose in a 5-L fermenter, the highest productivity and yield of L-serine from glucose reported to date. Transcriptome and intermediate metabolite were analyzed to further understand the regulatory mechanism of L-serine production. Conclusion: These results demonstrated that combined metabolic and bioprocess engineering strategies can improve L-serine productivity and yield, thus providing basic principles for rationally designing of high-yield production strains and paving the way for towards a simple and economical process for industrial L-serine production.


animal ◽  
2021 ◽  
pp. 100293
Author(s):  
J. Simões ◽  
J.A. Abecia ◽  
A. Cannas ◽  
J.A. Delgadillo ◽  
D. Lacasta ◽  
...  

2021 ◽  
Vol 9 (4) ◽  
pp. 797
Author(s):  
Davide Mugetti ◽  
Mattia Tomasoni ◽  
Paolo Pastorino ◽  
Giuseppe Esposito ◽  
Vasco Menconi ◽  
...  

The Mycobacterium fortuitum group (MFG) consists of about 15 species of fast-growing nontuberculous mycobacteria (NTM). These globally distributed microorganisms can cause diseases in humans and animals, especially fish. The increase in the number of species belonging to MFG and the diagnostic techniques panel do not allow to clarify their real clinical significance. In this study, biomolecular techniques were adopted for species determination of 130 isolates derived from fish initially identified through biochemical tests as NTM belonging to MFG. Specifically, gene sequencing and phylogenetic analysis were used based on a fragment of the gene encoding the 65 KDa heat shock protein (hsp65). The analyzes made it possible to confirm that all the isolates belong to MFG, allowing to identify the strains at species level. Phylogenetic analysis substantially confirmed what was obtained by gene sequencing, except for six strains; this is probably due to the sequences present in NCBI database. Although the methodology used cannot represent a univocal identification system, this study has allowed us to evaluate its effectiveness as regards the species of MFG. Future studies will be necessary to apply these methods with other gene fragments and to clarify the real pathogenic significance of the individual species of this group of microorganisms.


2021 ◽  
pp. 2101017
Author(s):  
Frank Mickoleit ◽  
Sabine Rosenfeldt ◽  
Mauricio Toro‐Nahuelpan ◽  
Miroslava Schaffer ◽  
Anna S. Schenk ◽  
...  

2012 ◽  
Vol 97 (8) ◽  
pp. 3343-3353 ◽  
Author(s):  
Claudia Korneli ◽  
Rebekka Biedendieck ◽  
Florian David ◽  
Dieter Jahn ◽  
Christoph Wittmann

2021 ◽  
Author(s):  
Benjamin Schmuck ◽  
Gabriele Greco ◽  
Andreas Barth ◽  
Nicola M. Pugno ◽  
Jan Johansson ◽  
...  

2017 ◽  
Vol 19 (20) ◽  
pp. 4804-4810 ◽  
Author(s):  
S. H. Shinde ◽  
C. V. Rode

A new and effective unique two-phase reaction system for the high yield production of tri(furyl)methane from furfural and furan.


ACS Nano ◽  
2009 ◽  
Vol 3 (12) ◽  
pp. 3839-3844 ◽  
Author(s):  
Sailaja Tetali ◽  
Mujtaba Zaka ◽  
Ronny Schönfelder ◽  
Alicja Bachmatiuk ◽  
Felix Börrnert ◽  
...  

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