Fermentation Processes to Produce Specialized Metabolites

A special issue of Fermentation (ISSN 2311-5637). This special issue belongs to the section "Fermentation Process Design".

Deadline for manuscript submissions: closed (30 June 2021) | Viewed by 10157

Special Issue Editors

Dipartimento di Biotecnologie e Scienze della Vita, Università degli Studi dell'Insubria, Via J.H. Dunant 3, 21100 Varese, Italy
Interests: actinomycetes; natural products; antibiotics; resistome; glycopeptides; lantibiotics
Special Issues, Collections and Topics in MDPI journals
Department of Biotechnology and Life Sciences, University of Insubria, via J.H. Dunant 3, 21100 Varese, Italy
Interests: actinomycetes; secondary metabolites; bioactive proteins; fermentation; isolation
Special Issues, Collections and Topics in MDPI journals
BioC-CheM Solutions Srl, Via R. Lepetit 34, 21040 Gerenzano, Italy
Interests: fungal metabolites; fungal enzymes; fungal proteomics; fungal biotechnology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Specialized metabolites or -referring to their traditional name- secondary metabolites are a heterogeneous group of compounds, naturally produced by an array of terrestrial and marine organisms, including plants, invertebrates, and microorganisms. These last (represented, for instance, by filamentous actinobacteria and fungi, as well as cyanobacteria, myxobacteria, and microalgae) are by far the most notable and prolific sources of bioactive molecules. Specialized metabolites greatly differ not only in their chemical structures, but also, and even more importantly, in their biological functions, which span from defence or competition, to signalling, symbiosis, metal transport, and much more. As a consequence, their potential applications cover various fields, such as nutraceuticals, agriculture, medicine, food and pharmaceutical industries. Notably, specialized metabolites with antibiotic or anticancer activity still constitute the preferential targets of screening campaigns, following the urge to discover new therapeutic candidates.
Due to their complex chemical structures, in many cases fermentation represents the only feasible process for the supply of these bioactive molecules, being chemical synthesis too complicated or too expensive. Improvement of fermentation conditions and design of enhanced bioprocesses and bioreactors are therefore essential to reduce production costs and achieve high quality standards.
The goal of this Special Issue is to describe (by original research articles or reviews) the impact of fermentation on the production of specialized metabolites of different origins.

Prof. Dr. Flavia Marinelli
Dr. Francesca Berini
Dr. Fabrizio Beltrametti
Guest Editors

Manuscript Submission Information

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Keywords

  • Specialized metabolites
  • Secondary metabolites
  • Antibiotics
  • Anticancers
  • Fermentation improvement
  • Bioprocesses
  • Bioreactors

Published Papers (4 papers)

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Research

10 pages, 1689 KiB  
Article
Heterogeneous A40926 Self-Resistance Profile in Nonomuraea gerenzanensis Population Informs Strain Improvement
Fermentation 2021, 7(3), 140; https://doi.org/10.3390/fermentation7030140 - 02 Aug 2021
Cited by 2 | Viewed by 1973
Abstract
Nonomuraea gerenzanensis ATCC 39727 produces the glycopeptide antibiotic A40926, which is the natural precursor of the semi-synthetic, last-resort drug dalbavancin. To reduce the cost of dalbavancin production, it is mandatory to improve the productivity of the producing strain. Here, we report that the [...] Read more.
Nonomuraea gerenzanensis ATCC 39727 produces the glycopeptide antibiotic A40926, which is the natural precursor of the semi-synthetic, last-resort drug dalbavancin. To reduce the cost of dalbavancin production, it is mandatory to improve the productivity of the producing strain. Here, we report that the exposure of N. gerenzanensis wild-type population to sub-inhibitory concentrations of A40926 led to the isolation of differently resistant phenotypes to which a diverse A40926 productivity was associated. The most resistant population (G, grand colonies) represented at least the 20% of the colonies growing on 2 µg/mL of A40926. It showed a stable phenotype after sub-culturing and a homogeneous profile of self-resistance to A40926 in population analysis profile (PAP) experiments. The less resistant population (P, petit) was represented by slow-growing colonies to which a lower A40926 productivity was associated. At bioreactor scale, the G variant produced twice more than the wild-type (ca. 400 mg/L A40926 versus less than 200 mg/L, respectively), paving the way for a rational strain improvement based on the selection of increasingly self-resistant colonies. Full article
(This article belongs to the Special Issue Fermentation Processes to Produce Specialized Metabolites)
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12 pages, 707 KiB  
Article
Production of Indole Auxins by Enterobacter sp. Strain P-36 under Submerged Conditions
Fermentation 2021, 7(3), 138; https://doi.org/10.3390/fermentation7030138 - 30 Jul 2021
Cited by 7 | Viewed by 2029
Abstract
Bioactive compounds produced by plant growth-promoting bacteria through a fermentation process can be valuable for developing innovative second-generation plant biostimulants. The purpose of this study is to investigate the biotechnological potential of Enterobacter on the production of auxin—a hormone with multiple roles in [...] Read more.
Bioactive compounds produced by plant growth-promoting bacteria through a fermentation process can be valuable for developing innovative second-generation plant biostimulants. The purpose of this study is to investigate the biotechnological potential of Enterobacter on the production of auxin—a hormone with multiple roles in plant growth and development. The experiments were carried in Erlenmeyer flasks and a 2-L fermenter under batch operating mode. The auxin production by Enterobacter sp. strain P-36 can be doubled by replacing casein with vegetable peptone in the culture medium. Cultivation of strain P36 in the benchtop fermenter indicates that by increasing the inoculum size 2-fold, it is possible to reduce the fermentation time from 72 (shake flask cultivation) to 24 h (bioreactor cultivation) and increase the auxin volumetric productivity from 6.4 to 17.2 mg [IAAequ]/L/h. Finally, an efficient storage procedure to preserve the bacterial auxin was developed. It is noteworthy that by sterilizing the clarified fermentation broth by filtration and storing the filtrated samples at +4 °C, the level of auxin remains unchanged for at least three months. Full article
(This article belongs to the Special Issue Fermentation Processes to Produce Specialized Metabolites)
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14 pages, 2519 KiB  
Article
Conversion of a Thiol Precursor into Aroma Compound 4-mercapto-4-methyl-2-pentanone Using Microbial Cell Extracts
Fermentation 2021, 7(3), 129; https://doi.org/10.3390/fermentation7030129 - 26 Jul 2021
Cited by 3 | Viewed by 2589
Abstract
4-Mercapto-4-methyl-2-pentanone (4MMP), a high-impact aroma compound with the box tree and black currant flavors was first identified in wines and could be released by microbial cysteine-S-conjugate β-lyases from its precursors. In this study, various yeasts and bacteria encoding β-lyases were selected to examine [...] Read more.
4-Mercapto-4-methyl-2-pentanone (4MMP), a high-impact aroma compound with the box tree and black currant flavors was first identified in wines and could be released by microbial cysteine-S-conjugate β-lyases from its precursors. In this study, various yeasts and bacteria encoding β-lyases were selected to examine their β-lyase activities. A thiol precursor of 4MMP, cysteine-conjugate of 4MMP (cys-4MMP), was synthesized with a purity of >95% in a relatively environmentally friendly approach, and its chemical structure was confirmed by nuclear magnetic resonance spectroscopy. The β-lyase activities of the crude cell extract from the bacteria and yeast strains for different substrates were examined using a colorimetric method. Shewanella putrefaciens cell extract exhibited the highest β-lyase activity for all tested substrates. Additionally, the optimum pH and temperature for their β-lyase activities were determined. To monitor the conversion efficiency of precursor cys-4MMP to 4MMP, liquid chromatography-mass spectrometry was used. Our data indicate that selected bacteria and yeasts could convert cys-4MMP into 4MMP, and S. putrefaciens exhibited the best conversion yield. This study demonstrated the potential use of microbial cell extracts to produce sulfur-containing aroma compounds such as 4MMP. Full article
(This article belongs to the Special Issue Fermentation Processes to Produce Specialized Metabolites)
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12 pages, 8461 KiB  
Article
Application of Extractive Fermentation on the Recuperation of Exopolysaccharide from Rhodotorula mucilaginosa UANL-001L
Fermentation 2020, 6(4), 108; https://doi.org/10.3390/fermentation6040108 - 13 Nov 2020
Cited by 2 | Viewed by 2036
Abstract
Exopolysaccharides (EPS) are high molecular weight biomaterials of industrial interest due to their variety of applications in the pharmaceutical, cosmetic, environmental, and food industries. EPS produced by Rhodotorula mucilaginosa UANL-001 L has sparked interest due to its bio-adsorbent and wide spectrum antimicrobial properties. [...] Read more.
Exopolysaccharides (EPS) are high molecular weight biomaterials of industrial interest due to their variety of applications in the pharmaceutical, cosmetic, environmental, and food industries. EPS produced by Rhodotorula mucilaginosa UANL-001 L has sparked interest due to its bio-adsorbent and wide spectrum antimicrobial properties. However, full exploitation and commercial application of EPS has been restrained due to low yields and high production costs. In the present work, the production and separation of EPS from Rhodotorula mucilaginosa UANL-001L was attempted through extractive fermentation in order to increase EPS production while simplifying the recovery process. Extractive fermentation was implemented with a thermoseparating polymer for phase formation (EOPO 970 and EOPO 12,000); culture viability, biomass generation, EPS production, rheological system properties, and phase formation time and temperature were monitored throughout the process. Extractive fermentation of Rhodotorula mucilaginosa UANL-001L with EOPO 970 resulted in a 42% EPS and 7% biomass recovery on the top phase after 5 to 13-min phase formation time and temperatures between 30 and 40 °C. This is the first report of extractive fermentation application for EPS production by yeast of the genera Rhodotorula, resulting in an interesting strategy for EPS production and recovery, although further optimization is needed. Full article
(This article belongs to the Special Issue Fermentation Processes to Produce Specialized Metabolites)
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