Research

19 pages, 1587 KiB

Open AccessArticle

Heterologous Production of β-Caryophyllene and Evaluation of Its Activity against Plant Pathogenic Fungi

by Fabienne Hilgers, Samer S. Habash, Anita Loeschcke, Yannic Sebastian Ackermann, Stefan Neumann, Achim Heck, Oliver Klaus, Jennifer Hage-Hülsmann, Florian M. W. Grundler, Karl-Erich Jaeger, A. Sylvia S. Schleker and Thomas Drepper

Microorganisms 2021, 9(1), 168; https://doi.org/10.3390/microorganisms9010168 - 14 Jan 2021

Cited by 14 | Viewed by 3335

Abstract

Terpenoids constitute one of the largest and most diverse groups within the class of secondary metabolites, comprising over 80,000 compounds. They not only exhibit important functions in plant physiology but also have commercial potential in the biotechnological, pharmaceutical, and agricultural sectors due to [...] Read more.

Terpenoids constitute one of the largest and most diverse groups within the class of secondary metabolites, comprising over 80,000 compounds. They not only exhibit important functions in plant physiology but also have commercial potential in the biotechnological, pharmaceutical, and agricultural sectors due to their promising properties, including various bioactivities against pathogens, inflammations, and cancer. In this work, we therefore aimed to implement the plant sesquiterpenoid pathway leading to β-caryophyllene in the heterologous host Rhodobacter capsulatus and achieved a maximum production of 139 ± 31 mg L⁻¹ culture. As this sesquiterpene offers various beneficial anti-phytopathogenic activities, we evaluated the bioactivity of β-caryophyllene and its oxygenated derivative β-caryophyllene oxide against different phytopathogenic fungi. Here, both compounds significantly inhibited the growth of Sclerotinia sclerotiorum and Fusarium oxysporum by up to 40%, while growth of Alternaria brassicicola was only slightly affected, and Phoma lingam and Rhizoctonia solani were unaffected. At the same time, the compounds showed a promising low inhibitory profile for a variety of plant growth-promoting bacteria at suitable compound concentrations. Our observations thus give a first indication that β-caryophyllene and β-caryophyllene oxide are promising natural agents, which might be applicable for the management of certain plant pathogenic fungi in agricultural crop production. Full article

(This article belongs to the Special Issue Microbial Secondary Metabolites and Biotechnology)

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20 pages, 3631 KiB

Open AccessArticle

Alternative Extraction and Characterization of Nitrogen-Containing Azaphilone Red Pigments and Ergosterol Derivatives from the Marine-Derived Fungal Talaromyces sp. 30570 Strain with Industrial Relevance

by Juliana Lebeau, Thomas Petit, Mireille Fouillaud, Laurent Dufossé and Yanis Caro

Microorganisms 2020, 8(12), 1920; https://doi.org/10.3390/microorganisms8121920 - 03 Dec 2020

Cited by 13 | Viewed by 2927

Abstract

Many species of Talaromyces of marine origin could be considered as non-toxigenic fungal cell factory. Some strains could produce water-soluble active biopigments in submerged cultures. These fungal pigments are of interest due to their applications in the design of new pharmaceutical products. In [...] Read more.

Many species of Talaromyces of marine origin could be considered as non-toxigenic fungal cell factory. Some strains could produce water-soluble active biopigments in submerged cultures. These fungal pigments are of interest due to their applications in the design of new pharmaceutical products. In this study, the azaphilone red pigments and ergosterol derivatives produced by a wild type of Talaromyces sp. 30570 (CBS 206.89 B) marine-derived fungal strain with industrial relevance were described. The strain was isolated from the coral reef of the Réunion island. An alternative extraction of the fungal pigments using high pressure with eco-friendly solvents was studied. Twelve different red pigments were detected, including two pigmented ergosterol derivatives. Nine metabolites were identified using HPLC-PDA-ESI/MS as Monascus-like azaphilone pigments. In particular, derivatives of nitrogen-containing azaphilone red pigment, like PP-R, 6-[(Z)-2-Carboxyvinyl]-N-GABA-PP-V, N-threonine-monascorubramin, N-glutaryl-rubropunctamin, monascorubramin, and presumed N-threonyl-rubropunctamin (or acid form of the pigment PP-R) were the major pigmented compounds produced. Interestingly, the bioproduction of these red pigments occurred only when complex organic nitrogen sources were present in the culture medium. These findings are important for the field of the selective production of Monascus-like azaphilone red pigments for the industries. Full article

(This article belongs to the Special Issue Microbial Secondary Metabolites and Biotechnology)

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14 pages, 8433 KiB

Open AccessArticle

Integrated Stirred-Tank Bioreactor with Internal Adsorption for the Removal of Ammonium to Enhance the Cultivation Performance of gdhA Derivative Pasteurella multocida B:2

by Siti Nur Hazwani Oslan, Joo Shun Tan, Sahar Abbasiliasi, Ahmad Ziad Sulaiman, Mohd Zamri Saad, Murni Halim and Arbakariya B. Ariff

Microorganisms 2020, 8(11), 1654; https://doi.org/10.3390/microorganisms8111654 - 24 Oct 2020

Cited by 5 | Viewed by 2863

Abstract

Growth of mutant gdhA Pasteurella multocida B:2 was inhibited by the accumulation of a by-product, namely ammonium in the culture medium during fermentation. The removal of this by-product during the cultivation of mutant gdhA P. multocida B:2 in a 2 L stirred-tank bioreactor [...] Read more.

Growth of mutant gdhA Pasteurella multocida B:2 was inhibited by the accumulation of a by-product, namely ammonium in the culture medium during fermentation. The removal of this by-product during the cultivation of mutant gdhA P. multocida B:2 in a 2 L stirred-tank bioreactor integrated with an internal column using cation-exchange adsorption resin for the improvement of cell viability was studied. Different types of bioreactor system (dispersed and internal) with resins were successfully used for ammonium removal at different agitation speeds. The cultivation in a bioreactor integrated with an internal column demonstrated a significant improvement in growth performance of mutant gdhA P. multocida B:2 (1.05 × 10¹¹ cfu/mL), which was 1.6-fold and 8.4-fold as compared to cultivation with dispersed resin (7.2 × 10¹⁰ cfu/mL) and cultivation without resin (1.25 × 10¹⁰ cfu/mL), respectively. The accumulation of ammonium in culture medium without resin (801 mg/L) was 1.24-fold and 1.37-fold higher than culture with dispersed resin (642.50 mg/L) and culture in the bioreactor integrated with internal adsorption (586.50 mg/L), respectively. Results from this study demonstrated that cultivation in a bioreactor integrated with the internal adsorption column in order to remove ammonium could reduce the inhibitory effect of this by-product and improve the growth performance of mutant gdhA P. multocida B:2. Full article

(This article belongs to the Special Issue Microbial Secondary Metabolites and Biotechnology)

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19 pages, 2571 KiB

Open AccessArticle

Screening Fungal Endophytes Derived from Under-Explored Egyptian Marine Habitats for Antimicrobial and Antioxidant Properties in Factionalised Textiles

by Ahmed A. Hamed, Sylvia Soldatou, M. Mallique Qader, Subha Arjunan, Kevin Jace Miranda, Federica Casolari, Coralie Pavesi, Oluwatofunmilay A. Diyaolu, Bathini Thissera, Manal Eshelli, Lassaad Belbahri, Lenka Luptakova, Nabil A. Ibrahim, Mohamed S. Abdel-Aziz, Basma M. Eid, Mosad A. Ghareeb, Mostafa E. Rateb and Rainer Ebel

Microorganisms 2020, 8(10), 1617; https://doi.org/10.3390/microorganisms8101617 - 21 Oct 2020

Cited by 38 | Viewed by 4696

Abstract

Marine endophytic fungi from under-explored locations are a promising source for the discovery of new bioactivities. Different endophytic fungi were isolated from plants and marine organisms collected from Wadi El-Natrun saline lakes and the Red Sea near Hurghada, Egypt. The isolated strains were [...] Read more.

Marine endophytic fungi from under-explored locations are a promising source for the discovery of new bioactivities. Different endophytic fungi were isolated from plants and marine organisms collected from Wadi El-Natrun saline lakes and the Red Sea near Hurghada, Egypt. The isolated strains were grown on three different media, and their ethyl acetate crude extracts were evaluated for their antimicrobial activity against a panel of pathogenic bacteria and fungi as well as their antioxidant properties. Results showed that most of the 32 fungal isolates initially obtained possessed antimicrobial and antioxidant activities. The most potent antimicrobial extracts were applied to three different cellulose containing fabrics to add new multifunctional properties such as ultraviolet protection and antimicrobial functionality. For textile safety, the toxicity profile of the selected fungal extract was evaluated on human fibroblasts. The 21 strains displaying bioactivity were identified on molecular basis and selected for chemical screening and dereplication, which was carried out by analysis of the MS/MS data using the Global Natural Products Social Molecular Networking (GNPS) platform. The obtained molecular network revealed molecular families of compounds commonly produced by fungal strains, and in combination with manual dereplication, further previously reported metabolites were identified as well as potentially new derivatives. Full article

(This article belongs to the Special Issue Microbial Secondary Metabolites and Biotechnology)

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16 pages, 716 KiB

Open AccessArticle

Evaluation of Filamentous Fungi and Yeasts for the Biodegradation of Sugarcane Distillery Wastewater

by Graziella Chuppa-Tostain, Melissa Tan, Laetitia Adelard, Alain Shum-Cheong-Sing, Jean-Marie François, Yanis Caro and Thomas Petit

Microorganisms 2020, 8(10), 1588; https://doi.org/10.3390/microorganisms8101588 - 15 Oct 2020

Cited by 13 | Viewed by 2645

Abstract

Sugarcane Distillery Spent Wash (DSW) is among the most pollutant industrial effluents, generally characterized by high Chemical Oxygen Demand (COD), high mineral matters and acidic pH, causing strong environmental impacts. Bioremediation is considered to be a good and cheap alternative to DSW treatment. [...] Read more.

Sugarcane Distillery Spent Wash (DSW) is among the most pollutant industrial effluents, generally characterized by high Chemical Oxygen Demand (COD), high mineral matters and acidic pH, causing strong environmental impacts. Bioremediation is considered to be a good and cheap alternative to DSW treatment. In this study, 37 strains of yeasts and filamentous fungi were performed to assess their potential to significantly reduce four parameters characterizing the organic load of vinasses (COD, pH, minerals and OD_475nm). In all cases, a pH increase (until a final pH higher than 8.5, being an increase superior to 3.5 units, as compared to initial pH) and a COD and minerals removal could be observed, respectively (until 76.53% using Aspergillus terreus var. africanus and 77.57% using Aspergillus niger). Depending on the microorganism, the OD_475nm could decrease (generally when filamentous fungi were used) or increase (generally when yeasts were used). Among the strains tested, the species from Aspergillus and Trametes genus offered the best results in the depollution of DSW. Concomitant with the pollutant load removal, fungal biomass, with yields exceeding 20 g·L⁻¹, was produced. Full article

(This article belongs to the Special Issue Microbial Secondary Metabolites and Biotechnology)

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17 pages, 3552 KiB

Open AccessArticle

Optimized Production of a Redox Metabolite (pyocyanin) by Pseudomonas aeruginosa NEJ01R Using a Maize By-Product

by Francisco Javier Bacame-Valenzuela, Jesús Alberto Pérez-Garcia, Mayra Leticia Figueroa-Magallón, Fabricio Espejel-Ayala, Luis Antonio Ortiz-Frade and Yolanda Reyes-Vidal

Microorganisms 2020, 8(10), 1559; https://doi.org/10.3390/microorganisms8101559 - 10 Oct 2020

Cited by 13 | Viewed by 2777

Abstract

Pseudomonas aeruginosa metabolizes pyocyanin, a redox molecule related to diverse biological activities. Culture conditions for the production of pyocyanin in a defined medium were optimized using a statistical design and response surface methodology. The obtained conditions were replicated using as substrate an alkaline [...] Read more.

Pseudomonas aeruginosa metabolizes pyocyanin, a redox molecule related to diverse biological activities. Culture conditions for the production of pyocyanin in a defined medium were optimized using a statistical design and response surface methodology. The obtained conditions were replicated using as substrate an alkaline residual liquid of cooked maize and its by-products. The untreated effluent (raw nejayote, RN) was processed to obtain a fraction without insoluble solids (clarified fraction, CL), then separated by a 30 kDa membrane where two fractions, namely, retentate (RE) and filtered (FI), were obtained. Optimal conditions in the defined medium were 29.6 °C, 223.7 rpm and pH = 6.92, which produced 2.21 μg mL⁻¹ of pyocyanin, and by using the wastewater, it was possible to obtain 3.25 μg mL⁻¹ of pyocyanin in the retentate fraction at 40 h. The retentate fraction presented the highest concentration of total solids related to the maximum concentration of pyocyanin (PYO) obtained. The pyocyanin redox behavior was analyzed using electrochemical techniques. In this way, valorization of lime-cooked maize wastewater (nejayote) used as a substrate was demonstrated in the production of a value-added compound, such as pyocyanin, a redox metabolite of Pseudomonas aeruginosa NEJ01R. Full article

(This article belongs to the Special Issue Microbial Secondary Metabolites and Biotechnology)

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9 pages, 1213 KiB

Open AccessArticle

High-Titer Lactic Acid Production by Pediococcus acidilactici PA204 from Corn Stover through Fed-Batch Simultaneous Saccharification and Fermentation

by Zhenting Zhang, Yanan Li, Jianguo Zhang, Nan Peng, Yunxiang Liang and Shumiao Zhao

Microorganisms 2020, 8(10), 1491; https://doi.org/10.3390/microorganisms8101491 - 28 Sep 2020

Cited by 16 | Viewed by 2683

Abstract

Lignocellulose comprised of cellulose and hemicellulose is one of the most abundant renewable feedstocks. Lactic acid bacteria have the ability to ferment sugar derived from lignocellulose. In this study, Pediococcus acidilactici PA204 is a lactic acid bacterium with a high tolerance of temperature [...] Read more.

Lignocellulose comprised of cellulose and hemicellulose is one of the most abundant renewable feedstocks. Lactic acid bacteria have the ability to ferment sugar derived from lignocellulose. In this study, Pediococcus acidilactici PA204 is a lactic acid bacterium with a high tolerance of temperature and high-efficiency utilization of xylose. We developed a fed-batch simultaneous saccharification and fermentation (SSF) process at 37 °C (pH 6.0) using the 30 FPU (filter paper units)/g cellulase and 20 g/L corn steep powder in a 5 L bioreactor to produce lactic acid (LA). The titer, yield, and productivity of LA produced from 12% (w/w) NaOH-pretreated and washed stover were 92.01 g/L, 0.77 g/g stover, and 1.28 g/L/h, respectively, and those from 15% NaOH-pretreated and washed stover were 104.11 g/L, 0.69 g/g stover, and 1.24 g/L/h, respectively. This study develops a feasible fed-batch SSF process for LA production from corn stover and provides a promising candidate strain for high-titer and -yield lignocellulose-derived LA production. Full article

(This article belongs to the Special Issue Microbial Secondary Metabolites and Biotechnology)

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14 pages, 456 KiB

Open AccessArticle

Influence of Culture Conditions and Medium Compositions on the Production of Bacteriocin-Like Inhibitory Substances by Lactococcus lactis Gh1

by Roslina Jawan, Sahar Abbasiliasi, Joo Shun Tan, Shuhaimi Mustafa, Murni Halim and Arbakariya B. Ariff

Microorganisms 2020, 8(10), 1454; https://doi.org/10.3390/microorganisms8101454 - 23 Sep 2020

Cited by 23 | Viewed by 3472

Abstract

Antibacterial peptides or bacteriocins produced by many strains of lactic acid bacteria have been used as food preservatives for many years without any known adverse effects. Bacteriocin titres can be modified by altering the physiological and nutritional factors of the producing bacterium to [...] Read more.

Antibacterial peptides or bacteriocins produced by many strains of lactic acid bacteria have been used as food preservatives for many years without any known adverse effects. Bacteriocin titres can be modified by altering the physiological and nutritional factors of the producing bacterium to improve the production in terms of yield and productivity. The effects of culture conditions (initial pH, inoculum age and inoculum size) and medium compositions (organic and inorganic nitrogen sources; carbon sources) were assessed for the production of bacteriocin-like inhibitory substances (BLIS) by Lactococcus lactis Gh1 in shake flask cultures. An inoculum of the mid-exponential phase culture at 1% (v/v) was the optimal age and size, while initial pH of culture media at alkaline and acidic state did not show a significant impact on BLIS secretion. Organic nitrogen sources were more favourable for BLIS production compared to inorganic sources. Production of BLIS by L. lactis Gh1 in soytone was 1.28-times higher as compared to that of organic nitrogen sources ((NH₄)2SO₄). The highest cell concentration (X_mX = 0.69 ± 0.026 g·L⁻¹) and specific growth rate (μ_max = 0.14 h⁻¹) were also observed in cultivation using soytone. By replacing carbon sources with fructose, BLIS production was increased up to 34.94% compared to BHI medium, which gave the biomass cell concentration and specific growth rate of 0.66 ± 0.002 g·L⁻¹ and 0.11 h⁻¹, respectively. It can be concluded that the fermentation factors have pronounced influences on the growth of L. lactis Gh1 and BLIS production. Results from this study could be used for subsequent application in process design and optimisation for improving BLIS production by L. lactis Gh1 at larger scale. Full article

(This article belongs to the Special Issue Microbial Secondary Metabolites and Biotechnology)

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16 pages, 1371 KiB

Open AccessArticle

Pentaminomycins C–E: Cyclic Pentapeptides as Autophagy Inducers from a Mealworm Beetle Gut Bacterium

by Sunghoon Hwang, Ly Thi Huong Luu Le, Shin-Il Jo, Jongheon Shin, Min Jae Lee and Dong-Chan Oh

Microorganisms 2020, 8(9), 1390; https://doi.org/10.3390/microorganisms8091390 - 10 Sep 2020

Cited by 17 | Viewed by 3131

Abstract

Pentaminomycins C–E (1–3) were isolated from the culture of the Streptomyces sp. GG23 strain from the guts of the mealworm beetle, Tenebrio molitor. The structures of the pentaminomycins were determined to be cyclic pentapeptides containing a modified amino [...] Read more.

Pentaminomycins C–E (1–3) were isolated from the culture of the Streptomyces sp. GG23 strain from the guts of the mealworm beetle, Tenebrio molitor. The structures of the pentaminomycins were determined to be cyclic pentapeptides containing a modified amino acid, N⁵-hydroxyarginine, based on 1D and 2D NMR and mass spectroscopic analyses. The absolute configurations of the amino acid residues were assigned using Marfey’s method and bioinformatics analysis of their nonribosomal peptide biosynthetic gene cluster (BGC). Detailed analysis of the BGC enabled us to propose that the structural variations in 1–3 originate from the low specificity of the adenylation domain in the nonribosomal peptide synthetase (NRPS) module 1, and indicate that macrocyclization can be catalyzed noncanonically by penicillin binding protein (PBP)-type TE. Furthermore, pentaminomycins C and D (1 and 2) showed significant autophagy-inducing activities and were cytoprotective against oxidative stress in vitro. Full article

(This article belongs to the Special Issue Microbial Secondary Metabolites and Biotechnology)

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20 pages, 5440 KiB

Open AccessArticle

Evaluation of Antiviral, Antibacterial and Antiproliferative Activities of the Endophytic Fungus Curvularia papendorfii, and Isolation of a New Polyhydroxyacid

by Afra Khiralla, Rosella Spina, Mihayl Varbanov, Stéphanie Philippot, Pascal Lemiere, Sophie Slezack-Deschaumes, Philippe André, Ietidal Mohamed, Sakina Mohamed Yagi and Dominique Laurain-Mattar

Microorganisms 2020, 8(9), 1353; https://doi.org/10.3390/microorganisms8091353 - 04 Sep 2020

Cited by 32 | Viewed by 3624

Abstract

An endophytic fungus isolated from Vernonia amygdalina, a medicinal plant from Sudan, was taxonomically characterized as Curvularia papendorfii. Ethyl acetate crude extract of C. papendorfii revealed an important antiviral effect against two viral pathogens, the human coronavirus HCoV 229E and a norovirus surrogate, [...] Read more.

An endophytic fungus isolated from Vernonia amygdalina, a medicinal plant from Sudan, was taxonomically characterized as Curvularia papendorfii. Ethyl acetate crude extract of C. papendorfii revealed an important antiviral effect against two viral pathogens, the human coronavirus HCoV 229E and a norovirus surrogate, the feline coronavirus FCV F9. For the last one, 40% of the reduction of the virus-induced cytopathogenic effect at lower multiplicity of infection (MOI) 0.0001 was observed. Selective antibacterial activity was obtained against Staphylococcus sp. (312 µg/mL), and interesting antiproliferative activity with half maximal inhibitory concentration (IC₅₀) value of 21.5 ± 5.9 µg/mL was observed against human breast carcinoma MCF7 cell line. Therefore, C. papendorfii crude extract was further investigated and fractionated. Twenty-two metabolites were identified by gas chromatography coupled to mass spectrometry (GC–MS), and two pure compounds, mannitol and a new polyhydroxyacid, called kheiric acid, were characterized. A combination of spectroscopic methods was used to elucidate the structure of the new aliphatic carboxylic acid: kheiric acid (3,7,11,15-tetrahydroxy-18-hydroxymethyl-14,16,20,22,24-pentamethyl-hexacosa-4E,8E,12E,16,18-pentaenoic acid). Kheiric acid showed an interesting result with a minimum inhibitory concentration (MIC) value of 62.5 µg/mL against meticillin-resistant Staphylococcus aureus (MRSA). Hence, endophytes associated with medicinal plants from Sudan merit more attention, as they could be a treasure of new bioactive compounds. Full article

(This article belongs to the Special Issue Microbial Secondary Metabolites and Biotechnology)

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23 pages, 1613 KiB

Open AccessArticle

Microorganisms Associated with the Marine Sponge Scopalina hapalia: A Reservoir of Bioactive Molecules to Slow Down the Aging Process

by Charifat Said Hassane, Mireille Fouillaud, Géraldine Le Goff, Aimilia D. Sklirou, Jean Bernard Boyer, Ioannis P. Trougakos, Moran Jerabek, Jérôme Bignon, Nicole J. de Voogd, Jamal Ouazzani, Anne Gauvin-Bialecki and Laurent Dufossé

Microorganisms 2020, 8(9), 1262; https://doi.org/10.3390/microorganisms8091262 - 20 Aug 2020

Cited by 17 | Viewed by 4583

Abstract

Aging research aims at developing interventions that delay normal aging processes and some related pathologies. Recently, many compounds and extracts from natural products have been shown to delay aging and/or extend lifespan. Marine sponges and their associated microorganisms have been found to produce [...] Read more.

Aging research aims at developing interventions that delay normal aging processes and some related pathologies. Recently, many compounds and extracts from natural products have been shown to delay aging and/or extend lifespan. Marine sponges and their associated microorganisms have been found to produce a wide variety of bioactive secondary metabolites; however, those from the Southwest of the Indian Ocean are much less studied, especially regarding anti-aging activities. In this study, the microbial diversity of the marine sponge Scopalina hapalia was investigated by metagenomic analysis. Twenty-six bacterial and two archaeal phyla were recovered from the sponge, of which the Proteobacteria phylum was the most abundant. In addition, thirty isolates from S. hapalia were selected and cultivated for identification and secondary metabolites production. The selected isolates were affiliated to the genera Bacillus, Micromonospora, Rhodoccocus, Salinispora, Aspergillus, Chaetomium, Nigrospora and unidentified genera related to the family Thermoactinomycetaceae. Crude extracts from selected microbial cultures were found to be active against seven targets i.e., elastase, tyrosinase, catalase, sirtuin 1, Cyclin-dependent kinase 7 (CDK7), Fyn kinase and proteasome. These results highlight the potential of microorganisms associated with a marine sponge from Mayotte to produce anti-aging compounds. Future work will focus on the isolation and the characterization of bioactive molecules. Full article

(This article belongs to the Special Issue Microbial Secondary Metabolites and Biotechnology)

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13 pages, 1949 KiB

Open AccessArticle

Comparative Study of the Proteins Involved in the Fermentation-Derived Compounds in Two Strains of Saccharomyces cerevisiae during Sparkling Wine Second Fermentation

by María del Carmen González-Jiménez, Teresa García-Martínez, Juan Carlos Mauricio, Irene Sánchez-León, Anna Puig-Pujol, Juan Moreno and Jaime Moreno-García

Microorganisms 2020, 8(8), 1209; https://doi.org/10.3390/microorganisms8081209 - 08 Aug 2020

Cited by 3 | Viewed by 2282

Abstract

Sparkling wine is a distinctive wine. Saccharomyces cerevisiae flor yeasts is innovative and ideal for the sparkling wine industry due to the yeasts’ resistance to high ethanol concentrations, surface adhesion properties that ease wine clarification, and the ability to provide a characteristic volatilome [...] Read more.

Sparkling wine is a distinctive wine. Saccharomyces cerevisiae flor yeasts is innovative and ideal for the sparkling wine industry due to the yeasts’ resistance to high ethanol concentrations, surface adhesion properties that ease wine clarification, and the ability to provide a characteristic volatilome and odorant profile. The objective of this work is to study the proteins in a flor yeast and a conventional yeast that are responsible for the production of the volatile compounds released during sparkling wine elaboration. The proteins were identified using the OFFGEL fractionator and LTQ Orbitrap. We identified 50 and 43 proteins in the flor yeast and the conventional yeast, respectively. Proteomic profiles did not show remarkable differences between strains except for Adh1p, Fba1p, Tdh1p, Tdh2p, Tdh3p, and Pgk1p, which showed higher concentrations in the flor yeast versus the conventional yeast. The higher concentration of these proteins could explain the fuller body in less alcoholic wines obtained when using flor yeasts. The data presented here can be thought of as a proteomic map for either flor or conventional yeasts which can be useful to understand how these strains metabolize the sugars and release pleasant volatiles under sparkling wine elaboration conditions. Full article

(This article belongs to the Special Issue Microbial Secondary Metabolites and Biotechnology)

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17 pages, 2917 KiB

Open AccessArticle

Bioactivity of Serratiochelin A, a Siderophore Isolated from a Co-Culture of Serratia sp. and Shewanella sp.

by Yannik Schneider, Marte Jenssen, Johan Isaksson, Kine Østnes Hansen, Jeanette Hammer Andersen and Espen H. Hansen

Microorganisms 2020, 8(7), 1042; https://doi.org/10.3390/microorganisms8071042 - 14 Jul 2020

Cited by 15 | Viewed by 3276

Abstract

Siderophores are compounds with high affinity for ferric iron. Bacteria produce these compounds to acquire iron in iron-limiting conditions. Iron is one of the most abundant metals on earth, and its presence is necessary for many vital life processes. Bacteria from the genus [...] Read more.

Siderophores are compounds with high affinity for ferric iron. Bacteria produce these compounds to acquire iron in iron-limiting conditions. Iron is one of the most abundant metals on earth, and its presence is necessary for many vital life processes. Bacteria from the genus Serratia contribute to the iron respiration in their environments, and previously several siderophores have been isolated from this genus. As part of our ongoing search for medicinally relevant compounds produced by marine microbes, a co-culture of a Shewanella sp. isolate and a Serratia sp. isolate, grown in iron-limited conditions, was investigated, and the rare siderophore serratiochelin A (1) was isolated with high yields. Compound 1 has previously been isolated exclusively from Serratia sp., and to our knowledge, there is no bioactivity data available for this siderophore to date. During the isolation process, we observed the degradation product serratiochelin C (2) after exposure to formic acid. Both 1 and 2 were verified by 1-D and 2-D NMR and high-resolution MS/MS. Here, we present the isolation of 1 from an iron-depleted co-culture of Shewanella sp. and Serratia sp., its proposed mechanism of degradation into 2, and the chemical and biological characterization of both compounds. The effects of 1 and 2 on eukaryotic and prokaryotic cells were evaluated, as well as their effect on biofilm formation by Staphylococcus epidermidis. While 2 did not show bioactivity in the given assays, 1 inhibited the growth of the eukaryotic cells and Staphylococcus aureus. Full article

(This article belongs to the Special Issue Microbial Secondary Metabolites and Biotechnology)

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17 pages, 4496 KiB

Open AccessArticle

Microbial Natural Products as Potential Inhibitors of SARS-CoV-2 Main Protease (M^pro)

by Ahmed M. Sayed, Hani A. Alhadrami, Ahmed O. El-Gendy, Yara I. Shamikh, Lassaad Belbahri, Hossam M. Hassan, Usama Ramadan Abdelmohsen and Mostafa E. Rateb

Microorganisms 2020, 8(7), 970; https://doi.org/10.3390/microorganisms8070970 - 29 Jun 2020

Cited by 55 | Viewed by 6511

Abstract

The main protease (M^pro) of the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was subjected to hyphenated pharmacophoric-based and structural-based virtual screenings using a library of microbial natural products (>24,000 compounds). Subsequent filtering of the resulted hits according to [...] Read more.

The main protease (M^pro) of the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was subjected to hyphenated pharmacophoric-based and structural-based virtual screenings using a library of microbial natural products (>24,000 compounds). Subsequent filtering of the resulted hits according to the Lipinski’s rules was applied to select only the drug-like molecules. Top-scoring hits were further filtered out depending on their ability to show constant good binding affinities towards the molecular dynamic simulation (MDS)-derived enzyme’s conformers. Final MDS experiments were performed on the ligand–protein complexes (compounds 1–12, Table S1) to verify their binding modes and calculate their binding free energy. Consequently, a final selection of six compounds (1–6) was proposed to possess high potential as anti-SARS-CoV-2 drug candidates. Our study provides insight into the role of the M^pro structural flexibility during interactions with the possible inhibitors and sheds light on the structure-based design of anti-coronavirus disease 2019 (COVID-19) therapeutics targeting SARS-CoV-2. Full article

(This article belongs to the Special Issue Microbial Secondary Metabolites and Biotechnology)

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20 pages, 3304 KiB

Open AccessArticle

Fermentative N-Methylanthranilate Production by Engineered Corynebacterium glutamicum

by Tatjana Walter, Nour Al Medani, Arthur Burgardt, Katarina Cankar, Lenny Ferrer, Anastasia Kerbs, Jin-Ho Lee, Melanie Mindt, Joe Max Risse and Volker F. Wendisch

Microorganisms 2020, 8(6), 866; https://doi.org/10.3390/microorganisms8060866 - 08 Jun 2020

Cited by 23 | Viewed by 4699

Abstract

The N-functionalized amino acid N-methylanthranilate is an important precursor for bioactive compounds such as anticancer acridone alkaloids, the antinociceptive alkaloid O-isopropyl N-methylanthranilate, the flavor compound O-methyl-N-methylanthranilate, and as a building block for peptide-based drugs. Current chemical [...] Read more.

The N-functionalized amino acid N-methylanthranilate is an important precursor for bioactive compounds such as anticancer acridone alkaloids, the antinociceptive alkaloid O-isopropyl N-methylanthranilate, the flavor compound O-methyl-N-methylanthranilate, and as a building block for peptide-based drugs. Current chemical and biocatalytic synthetic routes to N-alkylated amino acids are often unprofitable and restricted to low yields or high costs through cofactor regeneration systems. Amino acid fermentation processes using the Gram-positive bacterium Corynebacterium glutamicum are operated industrially at the million tons per annum scale. Fermentative processes using C. glutamicum for N-alkylated amino acids based on an imine reductase have been developed, while N-alkylation of the aromatic amino acid anthranilate with S-adenosyl methionine as methyl-donor has not been described for this bacterium. After metabolic engineering for enhanced supply of anthranilate by channeling carbon flux into the shikimate pathway, preventing by-product formation and enhancing sugar uptake, heterologous expression of the gene anmt encoding anthranilate N-methyltransferase from Ruta graveolens resulted in production of N-methylanthranilate (NMA), which accumulated in the culture medium. Increased SAM regeneration by coexpression of the homologous adenosylhomocysteinase gene sahH improved N-methylanthranilate production. In a test bioreactor culture, the metabolically engineered C. glutamicum C1* strain produced NMA to a final titer of 0.5 g·L⁻¹ with a volumetric productivity of 0.01 g·L⁻¹·h⁻¹ and a yield of 4.8 mg·g⁻¹ glucose. Full article

(This article belongs to the Special Issue Microbial Secondary Metabolites and Biotechnology)

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18 pages, 3026 KiB

Open AccessArticle

Actinomycetes from the Red Sea Sponge Coscinoderma mathewsi: Isolation, Diversity, and Potential for Bioactive Compounds Discovery

by Yara I. Shamikh, Aliaa A. El Shamy, Yasser Gaber, Usama Ramadan Abdelmohsen, Hashem A. Madkour, Hannes Horn, Hossam M. Hassan, Abeer H. Elmaidomy, Dalal Hussien M. Alkhalifah and Wael N. Hozzein

Microorganisms 2020, 8(5), 783; https://doi.org/10.3390/microorganisms8050783 - 23 May 2020

Cited by 20 | Viewed by 4933

Abstract

The diversity of actinomycetes associated with the marine sponge Coscinoderma mathewsi collected from Hurghada (Egypt) was studied. Twenty-three actinomycetes were separated and identified based on the 16S rDNA gene sequence analysis. Out of them, three isolates were classified as novel species of the [...] Read more.

The diversity of actinomycetes associated with the marine sponge Coscinoderma mathewsi collected from Hurghada (Egypt) was studied. Twenty-three actinomycetes were separated and identified based on the 16S rDNA gene sequence analysis. Out of them, three isolates were classified as novel species of the genera Micromonospora, Nocardia, and Gordonia. Genome sequencing of actinomycete strains has revealed many silent biosynthetic gene clusters and has shown their exceptional capacity for the production of secondary metabolites, not observed under classical cultivation conditions. Therefore, the effect of mycolic-acid-containing bacteria or mycolic acid on the biosynthesis of cryptic natural products was investigated. Sponge-derived actinomycete Micromonospora sp. UA17 was co-cultured using liquid fermentation with two mycolic acid-containing actinomycetes (Gordonia sp. UA19 and Nocardia sp. UA 23), or supplemented with pure mycolic acid. LC-HRESIMS data were analyzed to compare natural production across all crude extracts. Micromonospora sp. UA17 was rich with isotetracenone, indolocarbazole, and anthracycline analogs. Some co-culture extracts showed metabolites such as a chlorocardicin, neocopiamycin A, and chicamycin B that were not found in the respective monocultures, suggesting a mycolic acid effect on the induction of cryptic natural product biosynthetic pathways. The antibacterial, antifungal, and antiparasitic activities for the different cultures extracts were also tested. Full article

(This article belongs to the Special Issue Microbial Secondary Metabolites and Biotechnology)

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11 pages, 1661 KiB

Open AccessArticle

Novel Bi-Factorial Strategy against Candida albicans Viability Using Carnosic Acid and Propolis: Synergistic Antifungal Action

by Alejandra Argüelles, Ruth Sánchez-Fresneda, José P. Guirao-Abad, Cristóbal Belda, José Antonio Lozano, Francisco Solano and Juan-Carlos Argüelles

Microorganisms 2020, 8(5), 749; https://doi.org/10.3390/microorganisms8050749 - 16 May 2020

Cited by 11 | Viewed by 2322

Abstract

The potential fungicidal action of the natural extracts, carnosic acid (obtained from rosemary) and propolis (from honeybees’ panels) against the highly prevalent yeast Candida albicans, used herein as an archetype of pathogenic fungi, was tested. The separate addition of carnosic acid and [...] Read more.

The potential fungicidal action of the natural extracts, carnosic acid (obtained from rosemary) and propolis (from honeybees’ panels) against the highly prevalent yeast Candida albicans, used herein as an archetype of pathogenic fungi, was tested. The separate addition of carnosic acid and propolis on exponential cultures of the standard SC5314 C. albicans strain caused a moderate degree of cell death at relatively high concentrations. However, the combination of both extracts, especially in a 1:4 ratio, induced a potent synergistic pattern, leading to a drastic reduction in cell survival even at much lower concentrations. The result of a mathematical analysis by isobologram was consistent with synergistic action of the combined extracts rather than a merely additive effect. In turn, the capacity of SC5314 cells to form in vitro biofilms was also impaired by the simultaneous presence of both agents, supporting the potential application of carnosic acid and propolis mixtures in the prevention and treatment of clinical infections as an alternative to antibiotics and other antifungal agents endowed with reduced toxic side effects. Full article

(This article belongs to the Special Issue Microbial Secondary Metabolites and Biotechnology)

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19 pages, 2193 KiB

Open AccessArticle

Statistical Optimization of the Physico-Chemical Parameters for Pigment Production in Submerged Fermentation of Talaromyces albobiverticillius 30548

by Mekala Venkatachalam, Alain Shum-Chéong-Sing, Laurent Dufossé and Mireille Fouillaud

Microorganisms 2020, 8(5), 711; https://doi.org/10.3390/microorganisms8050711 - 11 May 2020

Cited by 19 | Viewed by 3311

Abstract

Talaromyces albobiverticillius 30548 is a marine-derived pigment producing filamentous fungus, isolated from the La Réunion island, in the Indian Ocean. The objective of this study was to examine and optimize the submerged fermentation (SmF) process parameters such as initial pH (4–9), temperature (21–27 [...] Read more.

Talaromyces albobiverticillius 30548 is a marine-derived pigment producing filamentous fungus, isolated from the La Réunion island, in the Indian Ocean. The objective of this study was to examine and optimize the submerged fermentation (SmF) process parameters such as initial pH (4–9), temperature (21–27 °C), agitation speed (100–200 rpm), and fermentation time (0–336 h), for maximum production of pigments (orange and red) and biomass, using the Box–Behnken Experimental Design and Response Surface Modeling (BBED and RSM). This methodology allowed consideration of multifactorial interactions between a set of parameters. Experiments were carried out based on the BBED using 250 mL shake flasks, with a 100 mL working volume of potato dextrose broth (PDB). From the experimental data, mathematical models were developed to predict the pigments and biomass yields. The individual and interactive effects of the process variables on the responses were also investigated (RSM). The optimal conditions for maximum production of pigments and biomass were derived by the numerical optimization method, as follows—initial pH of 6.4, temperature of 24 °C, agitation speed of 164 rpm, and fermentation time of 149 h, respectively. Full article

(This article belongs to the Special Issue Microbial Secondary Metabolites and Biotechnology)

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21 pages, 4088 KiB

Open AccessArticle

Baikalomycins A-C, New Aquayamycin-Type Angucyclines Isolated from Lake Baikal Derived Streptomyces sp. IB201691-2A

by Irina Voitsekhovskaia, Constanze Paulus, Charlotte Dahlem, Yuriy Rebets, Suvd Nadmid, Josef Zapp, Denis Axenov-Gribanov, Christian Rückert, Maxim Timofeyev, Jörn Kalinowski, Alexandra K. Kiemer and Andriy Luzhetskyy

Microorganisms 2020, 8(5), 680; https://doi.org/10.3390/microorganisms8050680 - 07 May 2020

Cited by 16 | Viewed by 4526

Abstract

Natural products produced by bacteria found in unusual and poorly studied ecosystems, such as Lake Baikal, represent a promising source of new valuable drug leads. Here we report the isolation of a new Streptomyces sp. strain IB201691-2A from the Lake Baikal endemic mollusk [...] Read more.

Natural products produced by bacteria found in unusual and poorly studied ecosystems, such as Lake Baikal, represent a promising source of new valuable drug leads. Here we report the isolation of a new Streptomyces sp. strain IB201691-2A from the Lake Baikal endemic mollusk Benedictia baicalensis. In the course of an activity guided screening three new angucyclines, named baikalomycins A–C, were isolated and characterized, highlighting the potential of poorly investigated ecological niches. Besides that, the strain was found to accumulate large quantities of rabelomycin and 5-hydroxy-rabelomycin, known shunt products in angucyclines biosynthesis. Baikalomycins A–C demonstrated varying degrees of anticancer activity. Rabelomycin and 5-hydroxy-rabelomycin further demonstrated antiproliferative activities. The structure elucidation showed that baikalomycin A is a modified aquayamycin with β-d-amicetose and two additional hydroxyl groups at unusual positions (6a and 12a) of aglycone. Baikalomycins B and C have alternating second sugars attached, α-l-amicetose and α-l-aculose, respectively. The gene cluster for baikalomycins biosynthesis was identified by genome mining, cloned using a transformation-associated recombination technique and successfully expressed in S. albus J1074. It contains a typical set of genes responsible for an angucycline core assembly, all necessary genes for the deoxy sugars biosynthesis, and three genes coding for the glycosyltransferase enzymes. Heterologous expression and deletion experiments allowed to assign the function of glycosyltransferases involved in the decoration of baikalomycins aglycone. Full article

(This article belongs to the Special Issue Microbial Secondary Metabolites and Biotechnology)

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9 pages, 3625 KiB

Open AccessCommunication

Antibiofilm Activity of a Trichoderma Metabolite against Xanthomonas campestris pv. campestris, Alone and in Association with a Phage

by Marina Papaianni, Annarita Ricciardelli, Andrea Fulgione, Giada d’Errico, Astolfo Zoina, Matteo Lorito, Sheridan L. Woo, Francesco Vinale and Rosanna Capparelli

Microorganisms 2020, 8(5), 620; https://doi.org/10.3390/microorganisms8050620 - 25 Apr 2020

Cited by 12 | Viewed by 3166

Abstract

Biofilm protects bacteria against the host’s immune system and adverse environmental conditions. Several studies highlight the efficacy of lytic phages in the prevention and eradication of bacterial biofilms. In this study, the lytic activity of Xccφ1 (Xanthomonas campestris pv. campestris-specific phage) [...] Read more.

Biofilm protects bacteria against the host’s immune system and adverse environmental conditions. Several studies highlight the efficacy of lytic phages in the prevention and eradication of bacterial biofilms. In this study, the lytic activity of Xccφ1 (Xanthomonas campestris pv. campestris-specific phage) was evaluated in combination with 6-pentyl-α-pyrone (a secondary metabolite produced by Trichoderma atroviride P1) and the mineral hydroxyapatite. Then, the antibiofilm activity of this interaction, called a φHA6PP complex, was investigated using confocal laser microscopy under static and dynamic conditions. Additionally, the mechanism used by the complex to modulate the genes (rpf, gumB, clp and manA) involved in the biofilm formation and stability was also studied. Our results demonstrated that Xccφ1, alone or in combination with 6PP and HA, interfered with the gene pathways involved in the formation of biofilm. This approach can be used as a model for other biofilm-producing bacteria. Full article

(This article belongs to the Special Issue Microbial Secondary Metabolites and Biotechnology)

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19 pages, 2787 KiB

Open AccessArticle

Comparative Transcriptomic Analysis Uncovers Genes Responsible for the DHA Enhancement in the Mutant Aurantiochytrium sp.

by Liangxu Liu, Zhangli Hu, Shuangfei Li, Hao Yang, Siting Li, Chuhan Lv, Madiha Zaynab, Christopher H. K. Cheng, Huapu Chen and Xuewei Yang

Microorganisms 2020, 8(4), 529; https://doi.org/10.3390/microorganisms8040529 - 07 Apr 2020

Cited by 23 | Viewed by 3395

Abstract

Docosahexaenoic acid (DHA), a n-3 long-chain polyunsaturated fatty acid, is critical for physiological activities of the human body. Marine eukaryote Aurantiochytrium sp. is considered a promising source for DHA production. Mutational studies have shown that ultraviolet (UV) irradiation (50 W, 30 s) [...] Read more.

Docosahexaenoic acid (DHA), a n-3 long-chain polyunsaturated fatty acid, is critical for physiological activities of the human body. Marine eukaryote Aurantiochytrium sp. is considered a promising source for DHA production. Mutational studies have shown that ultraviolet (UV) irradiation (50 W, 30 s) could be utilized as a breeding strategy for obtaining high-yield DHA-producing Aurantiochytrium sp. After UV irradiation (50 W, 30 s), the mutant strain X2 which shows enhanced lipid (1.79-fold, 1417.37 mg/L) and DHA (1.90-fold, 624.93 mg/L) production, was selected from the wild Aurantiochytrium sp. Instead of eicosapentaenoic acid (EPA), 9.07% of docosapentaenoic acid (DPA) was observed in the mutant strain X2. The comparative transcriptomic analysis showed that in both wild type and mutant strain, the fatty acid synthesis (FAS) pathway was incomplete with key desaturases, but genes related to the polyketide synthase (PKS) pathway were observed. Results presented that mRNA expression levels of CoAT, AT, ER, DH, and MT down-regulated in wild type but up-regulated in mutant strain X2, corresponding to the increased intercellular DHA accumulation. These findings indicated that CoAT, AT, ER, DH, and MT can be exploited for high DHA yields in Aurantiochytrium. Full article

(This article belongs to the Special Issue Microbial Secondary Metabolites and Biotechnology)

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Review

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25 pages, 3347 KiB

Open AccessReview

An Overview on Industrial and Medical Applications of Bio-Pigments Synthesized by Marine Bacteria

by Ali Nawaz, Rida Chaudhary, Zinnia Shah, Laurent Dufossé, Mireille Fouillaud, Hamid Mukhtar and Ikram ul Haq

Microorganisms 2021, 9(1), 11; https://doi.org/10.3390/microorganisms9010011 - 22 Dec 2020

Cited by 38 | Viewed by 11435

Abstract

Marine bacterial species contribute to a significant part of the oceanic population, which substantially produces biologically effectual moieties having various medical and industrial applications. The use of marine-derived bacterial pigments displays a snowballing effect in recent times, being natural, environmentally safe, and health [...] Read more.

Marine bacterial species contribute to a significant part of the oceanic population, which substantially produces biologically effectual moieties having various medical and industrial applications. The use of marine-derived bacterial pigments displays a snowballing effect in recent times, being natural, environmentally safe, and health beneficial compounds. Although isolating marine bacteria is a strenuous task, these are still a compelling subject for researchers, due to their promising avenues for numerous applications. Marine-derived bacterial pigments serve as valuable products in the food, pharmaceutical, textile, and cosmetic industries due to their beneficial attributes, including anticancer, antimicrobial, antioxidant, and cytotoxic activities. Biodegradability and higher environmental compatibility further strengthen the use of marine bio-pigments over artificially acquired colored molecules. Besides that, hazardous effects associated with the consumption of synthetic colors further substantiated the use of marine dyes as color additives in industries as well. This review sheds light on marine bacterial sources of pigmented compounds along with their industrial applicability and therapeutic insights based on the data available in the literature. It also encompasses the need for introducing bacterial bio-pigments in global pigment industry, highlighting their future potential, aiming to contribute to the worldwide economy. Full article

(This article belongs to the Special Issue Microbial Secondary Metabolites and Biotechnology)

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19 pages, 1008 KiB

Open AccessReview

Combating Parasitic Nematode Infections, Newly Discovered Antinematode Compounds from Marine Epiphytic Bacteria

by Nor Hawani Salikin, Jadranka Nappi, Marwan E. Majzoub and Suhelen Egan

Microorganisms 2020, 8(12), 1963; https://doi.org/10.3390/microorganisms8121963 - 11 Dec 2020

Cited by 9 | Viewed by 4362

Abstract

Parasitic nematode infections cause debilitating diseases and impede economic productivity. Antinematode chemotherapies are fundamental to modern medicine and are also important for industries including agriculture, aquaculture and animal health. However, the lack of suitable treatments for some diseases and the rise of nematode [...] Read more.

Parasitic nematode infections cause debilitating diseases and impede economic productivity. Antinematode chemotherapies are fundamental to modern medicine and are also important for industries including agriculture, aquaculture and animal health. However, the lack of suitable treatments for some diseases and the rise of nematode resistance to many available therapies necessitates the discovery and development of new drugs. Here, marine epiphytic bacteria represent a promising repository of newly discovered antinematode compounds. Epiphytic bacteria are ubiquitous on marine surfaces where they are under constant pressure of grazing by bacterivorous predators (e.g., protozoans and nematodes). Studies have shown that these bacteria have developed defense strategies to prevent grazers by producing toxic bioactive compounds. Although several active metabolites against nematodes have been identified from marine bacteria, drug discovery from marine microorganisms remains underexplored. In this review, we aim to provide further insight into the need and potential for marine epiphytic bacteria to become a new source of antinematode drugs. We discuss current and emerging strategies, including culture-independent high throughput screening and the utilization of Caenorhabditis elegans as a model target organism, which will be required to advance antinematode drug discovery and development from marine microbial sources. Full article

(This article belongs to the Special Issue Microbial Secondary Metabolites and Biotechnology)

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24 pages, 1695 KiB

Open AccessReview

Current Status and Future Strategies to Increase Secondary Metabolite Production from Cyanobacteria

by Yujin Jeong, Sang-Hyeok Cho, Hookeun Lee, Hyung-Kyoon Choi, Dong-Myung Kim, Choul-Gyun Lee, Suhyung Cho and Byung-Kwan Cho

Microorganisms 2020, 8(12), 1849; https://doi.org/10.3390/microorganisms8121849 - 24 Nov 2020

Cited by 19 | Viewed by 5543

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Microbial Secondary Metabolites and Biotechnology)

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Other

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9 pages, 419 KiB

Open AccessCommentary

Microbial Secondary Metabolism and Biotechnology

by Mireille Fouillaud and Laurent Dufossé

Microorganisms 2022, 10(1), 123; https://doi.org/10.3390/microorganisms10010123 - 07 Jan 2022

Cited by 11 | Viewed by 3568

Abstract

In recent decades scientific research has demonstrated that the microbial world is infinitely richer and more surprising than we could have imagined. Every day, new molecules produced by microorganisms are discovered, and their incredible diversity has not yet delivered all of its messages. [...] Read more.

In recent decades scientific research has demonstrated that the microbial world is infinitely richer and more surprising than we could have imagined. Every day, new molecules produced by microorganisms are discovered, and their incredible diversity has not yet delivered all of its messages. The current challenge of research is to select from the wide variety of characterized microorganisms and compounds, those which could provide rapid answers to crucial questions about human or animal health or more generally relating to society’s demands for medicine, pharmacology, nutrition or everyday well-being. Full article

(This article belongs to the Special Issue Microbial Secondary Metabolites and Biotechnology)

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8 pages, 607 KiB

Open AccessPerspective

Use of Permanent Wall-Deficient Cells as a System for the Discovery of New-to-Nature Metabolites

by Shraddha Shitut, Güniz Özer Bergman, Alexander Kros, Daniel E. Rozen and Dennis Claessen

Microorganisms 2020, 8(12), 1897; https://doi.org/10.3390/microorganisms8121897 - 30 Nov 2020

Cited by 5 | Viewed by 5042

Abstract

Filamentous actinobacteria are widely used as microbial cell factories to produce valuable secondary metabolites, including the vast majority of clinically relevant antimicrobial compounds. Secondary metabolites are typically encoded by large biosynthetic gene clusters, which allow for a modular approach to generating diverse compounds [...] Read more.

Filamentous actinobacteria are widely used as microbial cell factories to produce valuable secondary metabolites, including the vast majority of clinically relevant antimicrobial compounds. Secondary metabolites are typically encoded by large biosynthetic gene clusters, which allow for a modular approach to generating diverse compounds through recombination. Protoplast fusion is a popular method for whole genome recombination that uses fusion of cells that are transiently wall-deficient. This process has been applied for both inter- and intraspecies recombination. An important limiting step in obtaining diverse recombinants from fused protoplasts is regeneration of the cell wall, because this forces the chromosomes from different parental lines to segregate, thereby preventing further recombination. Recently, several labs have gained insight into wall-deficient bacteria that have the ability to proliferate without their cell wall, known as L-forms. Unlike protoplasts, L-forms can stably maintain multiple chromosomes over many division cycles. Fusion of such L-forms would potentially allow cells to express genes from both parental genomes while also extending the time for recombination, both of which can contribute to an increased chemical diversity. Here, we present a perspective on how L-form fusion has the potential to become a platform for novel compound discovery and may thus help to overcome the antibiotic discovery void. Full article

(This article belongs to the Special Issue Microbial Secondary Metabolites and Biotechnology)

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