Novel and Old Insights for Biotechnological Exploitation of Actinomycetota Strain Fermentations

A special issue of Fermentation (ISSN 2311-5637). This special issue belongs to the section "Microbial Metabolism, Physiology & Genetics".

Deadline for manuscript submissions: 30 April 2026 | Viewed by 3338

Special Issue Editor


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Guest Editor
1. Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, Palermo University, 90128 Palermo, Italy
2. NBFC, National Biodiversity Future Center, Piazza Marina 61, 90133 Palermo, Italy
Interests: morpho‑physiological and molecular characterization of strains belonging to the Actinomycetota phylum; analysis of membrane‑derived extracellular vesicles produced by streptomycetes; antibiotic production through fermentation of actinomycetotal strains; biosynthesis of microbial bioactive metabolites; analysis of antibiotic biosynthetic gene clusters; isolation and characterization of plant growth‑promoting bacteria; analysis and modulation of microbiomes from biotic or abiotic matrices, including sewage sludge, soil, and plant tissues

Special Issue Information

Dear Colleagues,

I would like to invite you to contribute to the Special Issue ‘Novel and Old Insights for Biotechnological Exploitation of Actinomycetota Strain Fermentations,’ which aims to bring together researchers worldwide to explore the diverse metabolic and biochemical potential of these bacteria.

Members of the phylum Actinomycetota (formerly known as Actinobacteria) are renowned for their biotechnological and industrial relevance, particularly for bioactive compound and enzyme production. Genera such as Streptomyces have historically played a pivotal role in the biosynthesis of valuable products. Today, omics-based approaches are revolutionizing our understanding of Actinomycetota biology, driving both traditional and innovative biotechnological applications. However, several challenges remain, including improving product yield and quality, as well as uncovering cryptic compounds.

This Special Issue welcomes contributions that highlight both classical and emerging approaches for fermenting well-studied or rare Actinomycetota strains, particularly focusing on the following topics: strain improvement, fermentation optimization, metabolic engineering, omics investigation, microbial interactions in co-cultures, extracellular vesicle isolation, biogenic nanomaterial production, and the discovery of novel bioactive compounds.

I encourage you to share your latest research to promote new perspectives and advance the knowledge in the field of Actinomycetota strain fermentation.

Best regards,

Dr. Giuseppe Gallo
Guest Editor

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Keywords

  • actinomycetota
  • actinobacteria
  • fermentation
  • biotechnological exploitation
  • metabolic engineering
  • bioactive compounds
  • strain improvement
  • omics studies
  • mixed cultures
  • enzyme production
  • microbial interactions

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Published Papers (4 papers)

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Research

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13 pages, 1714 KB  
Article
A Rare Actinomycete from Sicilian Soil: Antimicrobial Potential and Spore Conditioning-Driven Antibiotic Production in Kitasatospora sp. SeTe27
by Fanny Claire Capri, Enrico Tornatore, Andrea Firrincieli, Gemma Fernánez-García, Rosa Alduina, Angel Manteca and Alessandro Presentato
Fermentation 2026, 12(4), 185; https://doi.org/10.3390/fermentation12040185 - 3 Apr 2026
Viewed by 256
Abstract
Actinomycetes are among the richest sources of bioactive secondary metabolites in biotechnology, owing to their remarkable metabolic diversity. Although the genus Streptomyces has been extensively explored and has yielded many clinically important antibiotics, rare actinomycetes remain comparatively underinvestigated. In this study, Kitasatospora sp. [...] Read more.
Actinomycetes are among the richest sources of bioactive secondary metabolites in biotechnology, owing to their remarkable metabolic diversity. Although the genus Streptomyces has been extensively explored and has yielded many clinically important antibiotics, rare actinomycetes remain comparatively underinvestigated. In this study, Kitasatospora sp. SeTe27, isolated from uncontaminated soil in Sicily (Italy), was investigated for its antibacterial activity and fermentation-driven enhancement of secondary metabolite production. The strain inhibited Staphylococcus aureus ATCC 25923, prompting physiological and genomic analyses. Spore conditioning was evaluated in four media (R5A, GYM, TSB, and YEME) to enhance antibiotic production. Conditioned cultures exhibited markedly increased antibacterial activity in TSB and YEME, moderate production in R5A, and no detectable activity in GYM. Whole-genome sequencing revealed an 8.5 Mb genome (73.5% GC) containing 48 biosynthetic gene clusters (BGCs), including NRPS, PKS, terpene, and hybrid pathways. Several clusters showed high similarity to known antibiotic-associated BGCs, such as clifednamide- and phenazine-related pathways, while numerous orphan clusters indicated significant unexplored biosynthetic potential. These findings identify Kitasatospora sp. SeTe27 as a promising antimicrobial producer and demonstrate that spore conditioning in complex media is an effective strategy to enhance antibiotic production in rare actinomycetes. Full article
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18 pages, 7820 KB  
Article
Optimization of Fermentation and Mutagenesis for Enhanced Staurosporine Production in the Marine-Derived Streptomyces Strain OUCMDZ-3118
by Mingxing Zuo, Jiuman Xiang, Mingshen Zhang, Weiming Zhu and Liping Wang
Fermentation 2026, 12(2), 92; https://doi.org/10.3390/fermentation12020092 - 5 Feb 2026
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Abstract
Background: Staurosporine is a potent broad-spectrum alkaloid antibiotic originally isolated from Streptomyces sp. It is renowned for its strong inhibitory activity against protein kinases by competitively binding to their ATP-binding sites. Therefore, staurosporine and its derivatives have been extensively investigated for their potential [...] Read more.
Background: Staurosporine is a potent broad-spectrum alkaloid antibiotic originally isolated from Streptomyces sp. It is renowned for its strong inhibitory activity against protein kinases by competitively binding to their ATP-binding sites. Therefore, staurosporine and its derivatives have been extensively investigated for their potential as anticancer agents. However, a major challenge in its utilization is the low production yield in wild-type strains. To overcome this limitation, this study aimed to enhance staurosporine yield in marine-derived staurosporine-producing strain OUCMDZ-3118. Methods: The fermentation conditions were tested by single-factor experiment, Plackett–Burman experiment, steepest ascent path and Box–Benhnken response surface method. Subsequently, the ultraviolet mutagenesis was employed to generate high-yielding mutant strain. Results: The optimal culture conditions were 50 g/L rice, 50 g/L soybean powder, 3 g/L NaCl, 10 g/L L-tryptophan, inoculum concentration of 3% (v/v) in 150 mL of medium within a 500 mL flask, and fermentation time of 10 days. Following UV mutagenesis, the mutant strain produced a final staurosporine titer of 496 mg/L, an approximately 9.5-fold higher titer than that of the wild-type strain. In a 30-day solid-state fermentation under the conditions of 40 g rice, 40 g soybean powder, moistened with 80 mL water containing NaCl (3 g/L) and L-tryptophan (10 g/L), a yield of 578 mg per 80 g of substrate was also achieved. A consistent yield of 7.22 g/kg was achieved across approximately 1000 replicate fermentations under identical conditions, demonstrating the robustness of the process. Conclusions: This study yielded a stable, high-yielding strain for staurosporine production, paving the way for the development of staurosporine-based antitumor drugs and their derivatives. Full article
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15 pages, 2628 KB  
Article
Enhanced Cultivation of Actinomycetota Strains from Millipedes (Diplopoda) Using a Helper Strain-Assisted Method
by Yingying Shi, Eun-Young Seo, Jeffrey S. Owen, Zhaoyun He, Liufei Shi, Chang Yan, Wenhan Lin, Dawoon Jung and Shan He
Fermentation 2026, 12(1), 16; https://doi.org/10.3390/fermentation12010016 - 27 Dec 2025
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Abstract
The limited cultivability of Actinomycetota strains restricts the exploration of their novel antibiotics, highlighting the need for improved isolation techniques. This study employed a helper strain-assisted cultivation method which utilizes culture supernatants from helper strains to isolate diverse members of the Actinomycetota from [...] Read more.
The limited cultivability of Actinomycetota strains restricts the exploration of their novel antibiotics, highlighting the need for improved isolation techniques. This study employed a helper strain-assisted cultivation method which utilizes culture supernatants from helper strains to isolate diverse members of the Actinomycetota from millipedes and compared its efficacy with a standard method. Using a preliminary dual-layer solid media assay and subsequent confirmation experiments, eight helper strains (M3, M9, M13, N3, N4, N6, N8, and N9) were identified, whose supernatants promoted the growth of Actinomycetota and other microbes. Application of this method to millipede samples established a novel cultivation strategy based on co-cultivation with helper strains. The new method enabled the isolation of 233 bacterial species in total, of which 143 were species of the phylum Actinomycetota, including 49 novel species. In contrast, the standard method yielded only 42 total bacterial species and 29 species of Actinomycetota, with merely 8 novel species. Comparative diversity analysis revealed that the helper strain-assisted method yielded Actinomycetota strains from 85 genera, which was 3.5 times higher than the standard method. This demonstrates that the helper strain-assisted approach is a highly effective strategy for accessing diverse and novel microbial majority. Among the isolated Actinomycetota strains, 75 strains predicted to have high biosynthetic gene clusters (BGCs) numbers or expected to be novel species were screened for antibacterial activity. Fourteen strains (17%) exhibited inhibitory effects against at least one indicator bacterium. One novel strain, Streptomyces sp. N8-31, was selected for whole-genome sequencing. AntiSMASH analysis predicted 40 biosynthetic gene clusters in N8-31, with 60% showing less than 70% similarity to known clusters; among these, 20 clusters showed less than 50% similarity. These findings indicate that strain N8-31 is a rich reservoir of novel genetic resources, and its broad-spectrum antibacterial activity is likely linked to these unique secondary metabolite gene clusters. Critically, this study confirms that helper strain-assisted cultivation is a powerful tool for unlocking the hidden biosynthetic potential of previously inaccessible Actinomycetota. Full article
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Review

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21 pages, 1980 KB  
Review
Secondary Metabolites from Actinokineospora spp.: Insights into a Sparsely Studied Genus of Actinomycetes
by Oleksandr Yushchuk
Fermentation 2025, 11(12), 663; https://doi.org/10.3390/fermentation11120663 - 27 Nov 2025
Viewed by 982
Abstract
The genus Actinokineospora (family Pseudonocardiaceae) has recently emerged as a prolific source of structurally diverse, biologically active specialized metabolites. Actinokineospora spp. are filamentous actinomycetes isolated from various terrestrial biotopes. The genus is still sparsely represented taxonomically, with only 19 species holding validly [...] Read more.
The genus Actinokineospora (family Pseudonocardiaceae) has recently emerged as a prolific source of structurally diverse, biologically active specialized metabolites. Actinokineospora spp. are filamentous actinomycetes isolated from various terrestrial biotopes. The genus is still sparsely represented taxonomically, with only 19 species holding validly published names and genome sequences available for an additional six strains. Nevertheless, Actinokineospora appears to have one of the highest biosynthetic novelty index values among actinomycetes, making it a prime candidate for the discovery of new specialized metabolites. To date, several Actinokineospora strains have shown antimicrobial activity, including Actinokineospora acnipugnans R434T, Actinokineospora alba 03-9939T, Actinokineospora fastidiosa NRRL B-16697T, Actinokineospora riparia C-39162T, Actinokineospora sp. G85, and Actinokineospora sp. PR83; the active compounds from these strains remain to be identified and characterized. By contrast, detailed chemical characterization has been achieved for several producers: Actinokineospora spheciospongiae EG49T (polyketides actinospene and actinosporins; the lasso peptide actinokineosin), Actinokineospora bangkokensis 44EHWT (polyene thailandins), Actinokineospora fastidiosa ATCC 202099 (nocathiacin thiopeptides), Actinokineospora sp. UTMC 2448 (persiathiacin thiopeptides), and Actinokineospora auranticolor DSM 44650T (kineomіcin glycopeptides). Collectively, these findings establish Actinokineospora as a promising yet underexplored genus for antibiotic discovery and biosynthetic engineering. In this review, we summarize current knowledge on Actinokineospora spp. and provide an in-depth account of specialized metabolite production for those compounds whose structures have been elucidated. Full article
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