Sign in to use this feature.

Years

Between: -

Subjects

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Journals

Article Types

Countries / Regions

Search Results (44)

Search Parameters:
Keywords = hybrid PKS-NRPS

Order results
Result details
Results per page
Select all
Export citation of selected articles as:
23 pages, 4987 KB  
Article
Taxonomic and Genomic Characterization of Brevibacillus sp. JNUCC 42 from Baengnokdam Crater Lake, Mt. Halla, and Its Cosmeceutical Potential
by Jeong-Ha Lee, Mi-Yeon Moon, Mi-Sun Ko and Chang-Gu Hyun
Appl. Sci. 2025, 15(23), 12681; https://doi.org/10.3390/app152312681 - 29 Nov 2025
Viewed by 453
Abstract
Jeju Island, a volcanic island located off the southern coast of the Korean Peninsula, harbors highly specialized microbial communities shaped by its unique geological and climatic diversity. In particular, Baengnokdam Crater Lake at the summit of Mt. Halla represents an extreme, oligotrophic volcanic [...] Read more.
Jeju Island, a volcanic island located off the southern coast of the Korean Peninsula, harbors highly specialized microbial communities shaped by its unique geological and climatic diversity. In particular, Baengnokdam Crater Lake at the summit of Mt. Halla represents an extreme, oligotrophic volcanic habitat characterized by intense UV radiation, temperature fluctuations, and limited nutrients. From this environment, a novel bacterial strain, Brevibacillus sp. JNUCC 42, was isolated and subjected to comprehensive taxonomic, genomic, and biochemical analyses. The strain is a Gram-positive, aerobic, rod-shaped bacterium that grows optimally at 30 °C and pH 7.0–9.0 with moderate NaCl tolerance (≤3%). Phylogenetic analysis based on 16S rRNA gene sequencing and genome-scale GBDP confirmed its affiliation to the genus Brevibacillus, forming a distinct lineage closely related to B. laterosporus DSM 25T. Whole-genome sequencing generated a 4.93 Mb circular chromosome with a GC content of 40.7%. Comparative genomic analyses revealed ANI (87.1%) and dDDH (32.8%) values far below the species threshold, supporting its delineation as a novel species. Chemotaxonomic data further distinguished JNUCC 42 by its predominance of anteiso-C15:0 (37.24%) and iso-C15:0 (27.78%) fatty acids and the presence of a unique unidentified aminolipid not detected in the type strain. Genome mining identified 21 biosynthetic gene clusters, including NRPS, PKS, and NRPS–PKS hybrids, suggesting its potential to produce structurally diverse secondary metabolites. One of these metabolites, the cyclic dipeptide maculosin [cyclo(L-Pro-L-Tyr)], was purified from the culture extract and structurally characterized by NMR spectroscopy. Functional assays demonstrated that maculosin significantly inhibited α-MSH-induced melanogenesis and intracellular tyrosinase activity in B16F10 melanoma cells without cytotoxicity up to 100 µM. Collectively, these findings indicate that Brevibacillus sp. JNUCC 42 represents a novel species within the genus Brevibacillus and a promising microbial source of bioactive compounds with potential cosmeceutical applications. Full article
Show Figures

Figure 1

23 pages, 1790 KB  
Article
Genomic and Metabolomic Characterization of Kitasatospora griseola JNUCC 62 from Mulyeongari Oreum and Its Cosmeceutical Potential
by Mi-Sun Ko, Mi-Yeon Moon and Chang-Gu Hyun
Fermentation 2025, 11(12), 671; https://doi.org/10.3390/fermentation11120671 - 29 Nov 2025
Viewed by 731
Abstract
The actinobacterial strain Kitasatospora griseola JNUCC 62 was isolated from volcanic wetland soil at Mulyeongari Oreum, Jeju Island, and taxonomically identified through 16S rRNA gene and whole-genome analyses. The complete genome, assembled from PacBio Sequel I reads, spans 8.31 Mb with a GC [...] Read more.
The actinobacterial strain Kitasatospora griseola JNUCC 62 was isolated from volcanic wetland soil at Mulyeongari Oreum, Jeju Island, and taxonomically identified through 16S rRNA gene and whole-genome analyses. The complete genome, assembled from PacBio Sequel I reads, spans 8.31 Mb with a GC content of 72.8% and contains 7265 coding sequences. Comparative genomic indices (Average nucleotide identity, ANI 97.46%; digital DNA–DNA hybridization, dDDH 84.4%) confirmed its conspecific relationship with K. griseola JCM 3339T. Genome mining using antiSMASH 8.0 revealed 30 biosynthetic gene clusters (BGCs), including polyketide synthase (PKS), non-ribosomal peptide synthetase (NRPS), ribosomally synthesized and post-translationally modified peptide (RiPP), lanthipeptide, and terpene types, accounting for 18.6% of the genome. Several BGCs displayed homology to known formicamycin-, lankacidin-, and lanthipeptide-type clusters, while others were novel or cryptic, reflecting adaptation to the nutrient-poor volcanic environment. Ethyl acetate extraction of the culture broth, especially under tryptophan-supplemented conditions, yielded four metabolites—1-acetyl-β-carboline, perlolyrine, tryptopol, and 1H-pyrrole-2-carboxylic acid—identified by UV and NMR spectroscopy. These compounds correspond to NRPS–PKS hybrid and arylpolyene-type gene clusters predicted in the genome, suggesting precursor-directed biosynthesis of indole and pyrrole alkaloids. The ethyl acetate extract (JNUCC62 EA) exhibited strong antioxidant capacity in the ABTS assay, anti-inflammatory activity via inhibition of nitric oxide (31.09 ± 3.69% of control) and cytokines (IL-6, IL-1β, TNF-α) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, and anti-melanogenic effects in α-melanocyte-stimulating hormone (MSH)-stimulated B16F10 melanoma cells, where melanin content and tyrosinase activity decreased to 61.49 ± 1.24% and 24.32 ± 0.31% of the control, respectively, without cytotoxicity. A human primary skin irritation test confirmed no irritation up to 50 µg/mL, establishing excellent dermal safety. Collectively, these findings highlight K. griseola JNUCC 62 from Mulyeongari Oreum as a volcanic wetland-derived actinomycete harboring rich biosynthetic potential for novel indole alkaloids with antioxidant, anti-inflammatory, and whitening properties, supporting its development as a safe and multifunctional cosmeceutical ingredient. Full article
(This article belongs to the Special Issue Microbial Metabolism Focusing on Bioactive Molecules)
Show Figures

Figure 1

12 pages, 4263 KB  
Article
Characterization of a Novel Lentzea Species Isolated from the Kumtagh Desert and Genomic Insights into the Secondary Metabolite Potential of the Genus
by Ying Wen, Jiahui Li, Fujun Qiao, Wanyin Luo, Tuo Chen, Guangxiu Liu and Wei Zhang
Microorganisms 2025, 13(7), 1628; https://doi.org/10.3390/microorganisms13071628 - 10 Jul 2025
Viewed by 917
Abstract
A novel actinobacterial strain, designated E54T, was isolated from a hyper-arid desert soil sample collected from the Kumtagh Desert in Dunhuang, Gansu Province, China. Phylogenetic analysis based on 16S rRNA gene sequences placed strain E54T within the genus Lentzea, [...] Read more.
A novel actinobacterial strain, designated E54T, was isolated from a hyper-arid desert soil sample collected from the Kumtagh Desert in Dunhuang, Gansu Province, China. Phylogenetic analysis based on 16S rRNA gene sequences placed strain E54T within the genus Lentzea, showing highest similarity to Lentzea waywayandensis DSM 44232T (98.9%) and Lentzea flava NBRC 15743T (98.5%). However, whole-genome comparisons revealed that the average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) values between E54T and these related strains were below the thresholds for species delineation. Strain E54T exhibited typical morphological characteristics of the genus Lentzea, forming a branched substrate. It grew optimally at 28–30 °C, pH 7.0–9.0, and tolerated up to 10% NaCl. The cell wall contained meso-diaminopimelic acid, the predominant menaquinone was MK-9(H4), and major fatty acids included iso-C16:0. The polar lipid profile comprised diphosphatidyl glycerol, phosphatidyl ethanolamine, phosphatidyl inositol, hydroxyphosphatidyl ethanolamine, and an unidentified lipid. The characteristic amino acid type of the cell wall was meso-DAP. Whole-cell hydrolysis experiments revealed the characteristic cell wall sugar fractions: ribose and galactose. The genome of strain E54T is approximately 8.0 Mb with a DNA G+C content of 69.38 mol%. Genome mining revealed 39 biosynthetic gene clusters (BGCs), including non-ribosomal peptide synthetases (NRPS), polyketide synthases (PKS), terpenes, and siderophores. Comparative antiSMASH-based genome analysis across 38 Lentzea strains further demonstrated the genus’ remarkable biosynthetic diversity. NRPS and type I PKS (T1PKS) were the most prevalent BGC types, indicating a capacity to synthesize structurally complex and pharmacologically relevant metabolites. Together, these findings underscore the untapped biosynthetic potential of the genus Lentzea and support the proposal of strain E54T as a novel species. The strain E54T (=JCM 34936T = GDMCC 4.216T) should represent a novel species, for which the name Lentzea xerophila sp. nov. is proposed. Full article
(This article belongs to the Section Environmental Microbiology)
Show Figures

Figure 1

24 pages, 8248 KB  
Article
Genome-Guided Metabolomic Profiling of Peptaibol-Producing Trichoderma
by Arseniy A. Sinichich, Danil V. Krivonos, Anna A. Baranova, Mikhail Y. Zhitlov, Olga A. Belozerova, Vladislav A. Lushpa, Andrey V. Vvedensky, Marina V. Serebryakova, Anastasia I. Kalganova, Arsen M. Kudzhaev, Yuri A. Prokopenko, Sofia S. Sinelnikova, Ekaterina A. Trusova, Sergey I. Kovalchuk, Elena N. Ilina, Stanislav S. Terekhov and Vera A. Alferova
Int. J. Mol. Sci. 2025, 26(12), 5599; https://doi.org/10.3390/ijms26125599 - 11 Jun 2025
Cited by 2 | Viewed by 1641
Abstract
Peptaibols are linear fungal peptides featuring α,α-dialkylated amino acids (e.g., α-aminoisobutyric acid (Aib), isovaline (Iva)) and characteristic C-terminal alcohol groups. Despite their promising antibacterial and antiplasmodial activities, detailed biosynthetic studies remain limited. A genome-guided study of the fungus Trichodema sp. SK1-7, isolated from [...] Read more.
Peptaibols are linear fungal peptides featuring α,α-dialkylated amino acids (e.g., α-aminoisobutyric acid (Aib), isovaline (Iva)) and characteristic C-terminal alcohol groups. Despite their promising antibacterial and antiplasmodial activities, detailed biosynthetic studies remain limited. A genome-guided study of the fungus Trichodema sp. SK1-7, isolated from decaying wood, revealed the production of previously described trichorozin IV (1), along with novel SF4-type peptaibol 2 (trichorozin V). The structures of these compounds were elucidated through MS analysis, NMR study and advanced Marfey’s method. The genome of Trichoderma sp. SK1-7 harbors two PKS-NRPS hybrid gene clusters containing 14 and 18 adenylation domains. Analysis of the modular architecture suggested that trichorozins are synthesized by a 14-module protein via a module skipping mechanism. Genome mining revealed several types of short peptaibol synthase architectures (10–14 adenylation domains) across various Trichoderma species, accompanied by similar long peptaibol synthases. Furthermore, putative Aib/Iva biosynthesis machinery in Trichoderma was identified, showing specific architectures potentially involved in regulating peptaibol biosynthesis. Feeding experiments demonstrated that peptaibol production depends on the ratio of Iva/Aib. The isolated compounds exhibited moderate antibacterial and cytotoxic activities along with a synergistic effect when combined with membrane-targeting antibiotics. Our findings suggest that genome-guided approaches hold promise for further development of peptabiotics with a wide range of applications, including antibiotic adjuvants. Full article
Show Figures

Figure 1

19 pages, 2564 KB  
Article
Genomic Insights into Plant Growth-Promoting Traits of Lysinibacillus fusiformis and Bacillus cereus from Rice Fields in Panama
by Celestino Aguilar, Rito Herrera, José L. Causadías, Betzaida Bernal, Oris Chavarria, Claudia González, Jessica Gondola, Ambar Moreno and Alexander A. Martínez
Microbiol. Res. 2025, 16(5), 95; https://doi.org/10.3390/microbiolres16050095 - 7 May 2025
Viewed by 3074
Abstract
Soil, rhizosphere, and plant-associated microorganisms can enhance plant growth and health. A genomic analysis of these microbes revealed the key characteristics contributing to their beneficial effects. Following a field survey in Panama, four bacterial isolates with plant growth-promoting traits (PGPT) in rice ( [...] Read more.
Soil, rhizosphere, and plant-associated microorganisms can enhance plant growth and health. A genomic analysis of these microbes revealed the key characteristics contributing to their beneficial effects. Following a field survey in Panama, four bacterial isolates with plant growth-promoting traits (PGPT) in rice (Oryza sativa L.) were identified. In this study, we sequenced, assembled, and annotated the genomes of Lysinibacillus fusiformis C6 and 24, and Bacillus cereus D23 and 59. The C6 genome was 4,754,472 bp long with 10 contigs, 37.62% guanine-cytosine (GC) content, and 4657 coding sequences (CDS). The 24 genome was 4,683,219 bp with five contigs, 37.65% GC content, and 4550 CDS. The D23 genome was 6,199,908 bp long with 18 contigs, 34.84% GC content, and 6141 CDS. The 59 genome was 6,194,462 bp with 21 contigs, 34.87% GC content, and 6122 CDS. Digital DNA–DNA hybridization (dDDH) and average nucleotide identity (ANI) confirmed that C6 and 24 belong to Lysinibacillus fusiformis, whereas D23 and 59 belong to the Bacillus cereus species. Further results revealed that these bacteria contained genes characteristic of plant growth-promoting bacteria, such as siderophore, phytohormone auxin (IAA) production, and nitrogen-fixing abilities that promote plant growth. Moreover, the antiSMASH database identified gene clusters involved in secondary metabolite production (biosynthetic gene clusters), such as betalactone, NRPS-like, NRP-siderophore, terpene, and RiPP-like clusters. Moreover, diverse and novel biosynthetic clusters (BCGs) have included non-ribosomal peptides (NRPs), polyketides (PKs), bacteriocins, and ribosomally synthesized and post-transcriptionally modified peptides (RiPPs). This work offers new insights into the genomic basis of the studied strains’ plant growth-promoting capabilities. Full article
Show Figures

Figure 1

17 pages, 4865 KB  
Article
The PKS–NRPS Gene BBA_09856 Deletion Mutant of Beauveria bassiana Enhanced Its Virulence Against Ostrinia furnacalis Larvae and Strengthened the Host Plant’s Resistance to Botrytis cinerea as an Endotype
by Yanan Wang, Xiaowei Zou, Xiaomin Zhu, Ji Qi, Jianfeng Liu and Zhengkun Zhang
J. Fungi 2025, 11(3), 197; https://doi.org/10.3390/jof11030197 - 4 Mar 2025
Cited by 2 | Viewed by 1259
Abstract
Nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) play crucial roles in the development and pathogenicity of the entomopathogenic fungus Beauveria bassiana. However, they are among the few biosynthetic gene clusters with unknown functions in B. bassiana. To investigate the role [...] Read more.
Nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) play crucial roles in the development and pathogenicity of the entomopathogenic fungus Beauveria bassiana. However, they are among the few biosynthetic gene clusters with unknown functions in B. bassiana. To investigate the role of the hybrid PKS–NRPS synthetase gene BBA_09856 in B. bassiana, we constructed a mutant strain, ∆BBA09856-WT, by deleting the BBA_09856 gene through Agrobacterium-mediated transformation. We then analyzed the biological characteristics of the mutant strain and the virulence of the mutant strain toward Ostrinia furnacalis larvae, as well as its antagonistic effects against the phytopathogen Botrytis cinerea. We found that the average growth rate of the three mutant strains, ∆BBA09856-WT, was significantly higher compared to the wild-type (WT) strain on the 15th day of culture on potato dextrose agar (PDA) plates (7.01 cm vs. 6.30 cm, p < 0.01). Additionally, the average spore production(3.16 × 107/cm2 vs. 9.95 × 106/cm2, p < 0.001) and germination rate (82.50% vs. 54.72%, 12 h, p < 0.001) were significantly different between the three mutant strains, ∆BBA09856-WT, and the WT strain. The average survival rates of O. furnacalis infected with the WT strain and the three mutant strains, ∆BBA09856-WT, after 8 days were 61.66%, and 30.00%, respectively, indicating that the pathogenicity of the tested mutant strains was significantly greater than that of the WT strain. The results of the dual culture test indicated that the inhibitory rates of the WT and ∆BBA09856-WT strains against B. cinerea were 40.25% and 47.65%, respectively (p < 0.001). Similarly, in the dual culture test, the WT strain reduced the growth of B. cinerea by 9.90%, while the ∆BBA09856-WT exhibited a significantly greater inhibition rate of 28.29% (p < 0.05). The diameters of disease spots, measured 6 d after inoculation with B. cinerea in the tomato treatment groups, revealed significant differences in endophytic colonization between the WT and ∆BBA09856-WT strains in the WT+Bc and ∆BBA09856-WT+Bc treatment groups (15.26 mm vs. 12.16 mm, p < 0.01). Notably, ∆BBA09856-WT exhibited enhanced virulence toward O. furnacalis larvae and increased antagonistic activity against B. cinerea. Our results indicate that the gene BBA_09856 may have a negative correlation with the development and virulence of B. bassiana toward the insect pest O. furnacalis larvae, as well as its antagonism against B. cinerea. These findings suggest that molecular techniques, such as gene editing, could be employed to develop superior strains of B. bassiana for the biological control of plant diseases and insect pests. Full article
Show Figures

Figure 1

20 pages, 2561 KB  
Article
Exploration of Predicted Nitrogen-Containing Natural Products from Northern Canadian Bark Beetle-Associated Bacteria
by Nirasha Atapattu, Nicolas Justus, Hariniha Selvarajan, Mitzchilouise Baylosis, Marc Schieven and Kalindi D. Morgan
Nitrogen 2025, 6(1), 13; https://doi.org/10.3390/nitrogen6010013 - 3 Mar 2025
Viewed by 1877
Abstract
Bark beetle-associated bacteria from the sub-boreal and boreal forests of northern Canada represent a largely unexplored source of bioactive natural products. This study aims to investigate the chemical potential of bacteria isolated from Dendroctonus ponderosae, Dendroctonus rufipennis, Dendroctonus pseudotsugae, and [...] Read more.
Bark beetle-associated bacteria from the sub-boreal and boreal forests of northern Canada represent a largely unexplored source of bioactive natural products. This study aims to investigate the chemical potential of bacteria isolated from Dendroctonus ponderosae, Dendroctonus rufipennis, Dendroctonus pseudotsugae, and Ips perturbatus by focusing on nitrogen-containing secondary metabolites. Genomic analyses of the bacterial isolates identified diverse biosynthetic gene clusters (BGCs), including nonribosomal peptides (NRPs), NRPS-PKS hybrids, and ribosomally synthesized and post-translationally modified peptides (RiPPs), many of which exhibit low sequence homology, suggesting potential for novel bioactive compounds. Nitrogen-15 NMR spectroscopy was employed to detect nitrogen-containing functional groups in crude extracts, revealing distinct signals for amides, amines, and nitrogen heterocycles. The combination of BGC predictions and NMR data highlighted the genetic and chemical diversity of these bacteria and underscored the potential for discovering novel nitrogen-rich metabolites. These findings provide a foundation for further exploration of bioactive natural products with pharmaceutical and agrochemical applications and potential to contribute to the understanding of the chemical ecology of bark beetle–microbe interactions in northern ecosystems. Full article
Show Figures

Figure 1

11 pages, 1712 KB  
Article
Complete Genome Sequence of the Butirosin-Producing Bacillus vitellinus NBRC 13296 and Its Reclassification to Paenibacillus chitinolyticus
by Kyung-A. Hyun, Seung-Young Kim, Kyung-Hwan Boo, Won-Jae Chi and Chang-Gu Hyun
Microbiol. Res. 2024, 15(3), 1747-1757; https://doi.org/10.3390/microbiolres15030116 - 30 Aug 2024
Cited by 1 | Viewed by 1942
Abstract
Butirosins are naturally occurring aminoglycoside (AG) antibiotics featuring a 4,5-disubstituted 2-deoxystreptamine (2-DOS) with a (2S)-4-amino-2-hydroxybutyrate (AHBA) side chain. This side chain has been shown to confer resistance against AG-modifying enzymes, leading to ongoing studies on the butirosin biosynthetic pathway and the corresponding enzymes. [...] Read more.
Butirosins are naturally occurring aminoglycoside (AG) antibiotics featuring a 4,5-disubstituted 2-deoxystreptamine (2-DOS) with a (2S)-4-amino-2-hydroxybutyrate (AHBA) side chain. This side chain has been shown to confer resistance against AG-modifying enzymes, leading to ongoing studies on the butirosin biosynthetic pathway and the corresponding enzymes. Butirosin is produced by Niallia (formerly Bacillus) circulans and Bacillus vitellinus, with most research focused on the first strain. To date, no whole-genome analysis has been performed on B. vitellinus. In this study, we sequenced the complete genome of B. vitellinus NBRC 13296 and performed a comparative analysis of different butirosin biosyntheric gene clusters (BGCs), including those from N. circulans. The complete genome of B. vitellinus NBRC 13296 comprises a 6,331,192-base circular chromosome with GC content of 52.68%. The annotation revealed the presence of 5605 CDSs, 70 tRNA genes, 30 rRNA genes, and 3 ncRNA genes in NBRC 13296. The highest dDDH and ANI values between NBRC 13296 and the most closely related type strain, Paenibacillus chitinolyticus KCCM 41,400, were 97.8% and 98.66%, respectively. Based on these genome-based comparative analyses, we propose reclassifying B. vitellinus NBRC 13296 as P. chitinolyticus. Genome mining revealed 18 gene clusters encoding the biosynthesis of diverse secondary metabolites in the genome of B. vitellinus NBRC 13296, indicating the enormous biosynthetic potential of this strain. The predicted structural diversity of the secondary metabolites includes aminoglycosides, PKS, NRPS, PKS–NRPS hybrids, metallophores, phosphonates, terpenes, β-lactones, and RiPP peptides. We then comparatively characterized the butirosin BGCs previously studied in several N. circulans strains. Additionally, the comparative genome analysis revealed complete butirosin BGCs identified from P. chitinolyticus KCCM 41,400, P. chitinolyticus NRRL B-23119, P. chitinolyticus NRRL B-23120, P. chitinolyticus B-14908, P. chitinolyticus YSY-3.1, P. chitinolyticus JMW06, Paenibacillus sp. GbtcB18, Paenibacillus sp. HGH0039, and Paenibacillus sp. MZ04-78.2. Finally, we identified the core region consisting of BtrS, BtrN, BtrM, BtrL, BtrA, BtrB, BtrC, BtrD, BtrD, BtrE, BtrF, BtrG, BtrH, BtrI, BtrI, BtrJ, BtrK, BtrO, BtrP, and BtrV, followed by an upstream region organizing BtrQ, BtrW, BtrX, BtrY, and BtrZ in the same transcriptional direction and sequential genetic arrangement, and a downstream region organizing various proteins based on BtrT, BtrR2, BtrU, and BtrR1. Our study provides insights into the reclassification of B. vitellinus NBRC 13296 to P. chitinolyticus and suggests the need for continued studies on butirosin biosynthesis from an enzymatic perspective. Full article
Show Figures

Figure 1

16 pages, 2900 KB  
Article
Chalkophomycin Biosynthesis Revealing Unique Enzyme Architecture for a Hybrid Nonribosomal Peptide Synthetase and Polyketide Synthase
by Long Yang, Liwei Yi, Bang Gong, Lili Chen, Miao Li, Xiangcheng Zhu, Yanwen Duan and Yong Huang
Molecules 2024, 29(9), 1982; https://doi.org/10.3390/molecules29091982 - 25 Apr 2024
Cited by 4 | Viewed by 2420
Abstract
Chalkophomycin is a novel chalkophore with antibiotic activities isolated from Streptomyces sp. CB00271, while its potential in studying cellular copper homeostasis makes it an important probe and drug lead. The constellation of N-hydroxylpyrrole, 2H-oxazoline, diazeniumdiolate, and methoxypyrrolinone functional groups into [...] Read more.
Chalkophomycin is a novel chalkophore with antibiotic activities isolated from Streptomyces sp. CB00271, while its potential in studying cellular copper homeostasis makes it an important probe and drug lead. The constellation of N-hydroxylpyrrole, 2H-oxazoline, diazeniumdiolate, and methoxypyrrolinone functional groups into one compact molecular architecture capable of coordinating cupric ions draws interest to unprecedented enzymology responsible for chalkophomycin biosynthesis. To elucidate the biosynthetic machinery for chalkophomycin production, the chm biosynthetic gene cluster from S. sp. CB00271 was identified, and its involvement in chalkophomycin biosynthesis was confirmed by gene replacement. The chm cluster was localized to a ~31 kb DNA region, consisting of 19 open reading frames that encode five nonribosomal peptide synthetases (ChmHIJLO), one modular polyketide synthase (ChmP), six tailoring enzymes (ChmFGMNQR), two regulatory proteins (ChmAB), and four resistance proteins (ChmA′CDE). A model for chalkophomycin biosynthesis is proposed based on functional assignments from sequence analysis and structure modelling, and is further supported by analogy to over 100 chm-type gene clusters in public databases. Our studies thus set the stage to fully investigate chalkophomycin biosynthesis and to engineer chalkophomycin analogues through a synthetic biology approach. Full article
Show Figures

Figure 1

25 pages, 38527 KB  
Article
Molecular Phylogenetic and Comparative Genomic Analysis of Pleurocordyceps fusiformispora sp. nov. and Perennicordyceps elaphomyceticola in the Family Polycephalomycetaceae
by Zuoheng Liu, Yingling Lu, Dexiang Tang, Juye Zhu, Lijun Luo, Yue Chen and Hong Yu
J. Fungi 2024, 10(4), 297; https://doi.org/10.3390/jof10040297 - 19 Apr 2024
Viewed by 2434
Abstract
Several Pleurocordyceps species have been reported as hyperparasitic fungi. A new species, Pleurocordyceps fusiformispora, and a known species, Perennicordyceps elaphomyceticola, are described here based on morphology and phylogenetic evidence from six genes (ITS, SSU, LSU, TET1-α, RPB1, and RPB2 [...] Read more.
Several Pleurocordyceps species have been reported as hyperparasitic fungi. A new species, Pleurocordyceps fusiformispora, and a known species, Perennicordyceps elaphomyceticola, are described here based on morphology and phylogenetic evidence from six genes (ITS, SSU, LSU, TET1-α, RPB1, and RPB2). Pl. fusiformispora differed from the other Pleurocordyceps species by producing flaky colonies, ovoid or elliptic α-conidia, and fusiform or long fusiform β-conidia. Both full genomes of Pe. elaphomyceticola and Pl. fusiformispora were sequenced, annotated, and compared. The antiSMASH and local BLAST analyses revealed significant differences in the number and types of putative secondary metabolite biosynthetic gene clusters, i.e., NPPS, PKS, and hybrid PKS–NRPS domains, between the two species. In addition, the putative BGCs of six compounds, namely ε-poly lysine, 4-epi-15-epi-brefeldin A, Monorden D/monocillin IV/monocillin VII/pochonin M/monocillin V/monocillin II, Tolypyridone, Piperazine, and Triticone DABFC, were excavated in the present study. This study motivates the use of heterologous expression and gene knockout methods to discover novel biologically active SMs from Polycephalomycetaceae. Full article
Show Figures

Figure 1

13 pages, 1133 KB  
Article
Analysis of the Mycotoxin Levels and Expression Pattern of SWN Genes at Different Time Points in the Fungus Slafractonia leguminicola
by Sumanjari Das, Dale R. Gardner, Daniel Cook and Rebecca Creamer
Microorganisms 2024, 12(4), 670; https://doi.org/10.3390/microorganisms12040670 - 27 Mar 2024
Viewed by 2122
Abstract
The fungal plant pathogen Slafractonia leguminicola produces two mycotoxins that affect animals: slaframine, which causes slobbers, and swainsonine, which causes locoism. Slafractonia leguminicola contains the swainsonine-associated orthologous gene clusters, “SWN”, which include a multifunctional swnK gene (NRPS-PKS hybrid), swnH1 and swnH2 (nonheme iron [...] Read more.
The fungal plant pathogen Slafractonia leguminicola produces two mycotoxins that affect animals: slaframine, which causes slobbers, and swainsonine, which causes locoism. Slafractonia leguminicola contains the swainsonine-associated orthologous gene clusters, “SWN”, which include a multifunctional swnK gene (NRPS-PKS hybrid), swnH1 and swnH2 (nonheme iron dioxygenase genes), swnN and swnR (reductase genes), and swnT (transmembrane transporter). In addition to these genes, two paralogs of swnK, swnK1 (paralog1) and swnk2 (paralog2), are found in S. leguminicola. cDNAs from total mRNA were isolated from the S. leguminicola mycelia grown in the culture plates as well as from leaves inoculated with the fungal mycelia at different time points, and expression pattern of the SWN genes were analyzed using RT-qPCR. The concentrations of swainsonine and slaframine production from this fungus at different time points were also examined using liquid chromatography–mass spectrometry. The timing of gene expression was similar in cultured fungus and inoculated leaves and agreed with our proposed biosynthetic pathway. Substantially more swainsonine was produced than slaframine during time course studies. Full article
(This article belongs to the Special Issue Fungal Biology and Interactions, 2nd Edition)
Show Figures

Figure 1

16 pages, 2220 KB  
Article
Unearthing a Cryptic Biosynthetic Gene Cluster for the Piperazic Acid-Bearing Depsipeptide Diperamycin in the Ant-Dweller Streptomyces sp. CS113
by Coral García-Gutiérrez, Ignacio Pérez-Victoria, Ignacio Montero, Jorge Fernández-De la Hoz, Mónica G. Malmierca, Jesús Martín, José A. Salas, Carlos Olano, Fernando Reyes and Carmen Méndez
Int. J. Mol. Sci. 2024, 25(4), 2347; https://doi.org/10.3390/ijms25042347 - 16 Feb 2024
Cited by 5 | Viewed by 3413
Abstract
Piperazic acid is a cyclic nonproteinogenic amino acid that contains a hydrazine N-N bond formed by a piperazate synthase (KtzT-like). This amino acid, found in bioactive natural products synthesized by non-ribosomal peptide synthetases (NRPSs), confers conformational constraint to peptides, an important feature for [...] Read more.
Piperazic acid is a cyclic nonproteinogenic amino acid that contains a hydrazine N-N bond formed by a piperazate synthase (KtzT-like). This amino acid, found in bioactive natural products synthesized by non-ribosomal peptide synthetases (NRPSs), confers conformational constraint to peptides, an important feature for their biological activities. Genome mining of Streptomyces strains has been revealed as a strategy to identify biosynthetic gene clusters (BGCs) for potentially active compounds. Moreover, the isolation of new strains from underexplored habitats or associated with other organisms has allowed to uncover new BGCs for unknown compounds. The in-house “Carlos Sialer (CS)” strain collection consists of seventy-one Streptomyces strains isolated from the cuticle of leaf-cutting ants of the tribe Attini. Genomes from twelve of these strains have been sequenced and mined using bioinformatics tools, highlighting their potential to encode secondary metabolites. In this work, we have screened in silico those genomes, using KtzT as a hook to identify BGCs encoding piperazic acid-containing compounds. This resulted in uncovering the new BGC dpn in Streptomyces sp. CS113, which encodes the biosynthesis of the hybrid polyketide–depsipeptide diperamycin. Analysis of the diperamycin polyketide synthase (PKS) and NRPS reveals their functional similarity to those from the aurantimycin A biosynthetic pathway. Experimental proof linking the dpn BGC to its encoded compound was achieved by determining the growth conditions for the expression of the cluster and by inactivating the NRPS encoding gene dpnS2 and the piperazate synthase gene dpnZ. The identity of diperamycin was confirmed by High-Resolution Mass Spectrometry (HRMS) and Nuclear Magnetic Resonance (NMR) and by analysis of the domain composition of modules from the DpnP PKS and DpnS NRPS. The identification of the dpn BGC expands the number of BGCs that have been confirmed to encode the relatively scarcely represented BGCs for depsipeptides of the azinothricin family of compounds and will facilitate the generation of new-to-nature analogues by combinatorial biosynthesis. Full article
(This article belongs to the Collection Feature Papers in Molecular Microbiology)
Show Figures

Figure 1

14 pages, 2329 KB  
Article
Profile of PKS and NRPS Gene Clusters in the Genome of Streptomyces cellostaticus NBRC 12849T
by Hisayuki Komaki and Tomohiko Tamura
Fermentation 2023, 9(11), 924; https://doi.org/10.3390/fermentation9110924 - 24 Oct 2023
Cited by 6 | Viewed by 3858
Abstract
Polyketides and nonribosomal peptides are major secondary metabolites in members of the genus Streptomyces. Streptomyces cellostaticus is a validly recognized species and the type strain produces cellostatin. However, little is known about whether it has the potential to produce diverse polyketides and [...] Read more.
Polyketides and nonribosomal peptides are major secondary metabolites in members of the genus Streptomyces. Streptomyces cellostaticus is a validly recognized species and the type strain produces cellostatin. However, little is known about whether it has the potential to produce diverse polyketides and nonribosomal peptides. Here, we sequenced the whole genome of S. cellostaticus NBRC 12849T and surveyed polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) gene clusters in the genome. The genome encoded 12 PKS, one NRPS and eight hybrid PKS/NRPS gene clusters. Among the 21 gene clusters, products of 10 gene clusters were annotated to be an annimycin congener, fuelimycins, lankamycin, streptovaricin, spore pigment, flaviolin, foxicin, blasticidin, lankacidin and an incarnatapeptine congener via our bioinformatic analysis. Although the other clusters were orphan and their products were unknown, five of them were predicted to be compounds derived from two independent diketides, a tridecaketide, a triketide and a tetraketide with a cysteine residue, respectively. These results suggest that S. cellostaticus is a source of diverse polyketides and hybrid polyketide/nonribosomal peptides, including unknown and new secondary metabolites. Full article
(This article belongs to the Special Issue Bioactive Metabolites of Bacterial Origin)
Show Figures

Figure 1

13 pages, 3329 KB  
Article
The Pangenome of Gram-Negative Environmental Bacteria Hides a Promising Biotechnological Potential
by Cláudia Covas, Gonçalo Figueiredo, Margarida Gomes, Tiago Santos, Sónia Mendo and Tânia S. Caetano
Microorganisms 2023, 11(10), 2445; https://doi.org/10.3390/microorganisms11102445 - 29 Sep 2023
Cited by 5 | Viewed by 2873
Abstract
Secondary metabolites (SMs) from environmental bacteria offer viable solutions for various health and environmental challenges. Researchers are employing advanced bioinformatic tools to investigate less-explored microorganisms and unearth novel bioactive compounds. In this research area, our understanding of SMs from environmental Gram-negative bacteria lags [...] Read more.
Secondary metabolites (SMs) from environmental bacteria offer viable solutions for various health and environmental challenges. Researchers are employing advanced bioinformatic tools to investigate less-explored microorganisms and unearth novel bioactive compounds. In this research area, our understanding of SMs from environmental Gram-negative bacteria lags behind that of its Gram-positive counterparts. In this regard, Pedobacter spp. have recently gained attention, not only for their role as plant growth promoters but also for their potential in producing antimicrobials. This study focuses on the genomic analysis of Pedobacter spp. to unveil the diversity of the SMs encoded in their genomes. Among the 41 genomes analyzed, a total of 233 biosynthetic gene clusters (BGCs) were identified, revealing the potential for the production of diverse SMs, including RiPPs (27%), terpenes (22%), hybrid SMs (17%), PKs (12%), NRPs (9%) and siderophores (6%). Overall, BGC distribution did not correlate with phylogenetic lineage and most of the BGCs showed no significant hits in the MIBiG database, emphasizing the uniqueness of the compounds that Pedobacter spp. can produce. Of all the species examined, P. cryoconitis and P. lusitanus stood out for having the highest number and diversity of BGCs. Focusing on their applicability and ecological functions, we investigated in greater detail the BGCs responsible for siderophore and terpenoid production in these species and their relatives. Our findings suggest that P. cryoconitis and P. lusitanus have the potential to produce novel mixtures of siderophores, involving bifunctional IucAC/AcD NIS synthetases, as well as carotenoids and squalene. This study highlights the biotechnological potential of Pedobacter spp. in medicine, agriculture and other industries, emphasizing the need for a continued exploration of its SMs and their applications. Full article
(This article belongs to the Special Issue Bacterial and Antibiotic Resistance in the Environment)
Show Figures

Figure 1

13 pages, 1409 KB  
Article
Taxonogenomic Analysis of Marine-Derived Streptomyces sp. N11-50 and the Profile of NRPS and PKS Gene Clusters
by Hisayuki Komaki, Yasuhiro Igarashi and Tomohiko Tamura
Hydrobiology 2023, 2(2), 382-394; https://doi.org/10.3390/hydrobiology2020025 - 2 Jun 2023
Cited by 3 | Viewed by 2782
Abstract
Streptomyces sp. N11-50 was isolated from deep-sea water and found to produce diketopiperazine (DKP) compounds such as albonoursin and cyclo(Phe-Leu). This study aimed to reveal the potential to synthesize diverse nonribosomal peptide and polyketide compounds as the other secondary metabolites different from DKP [...] Read more.
Streptomyces sp. N11-50 was isolated from deep-sea water and found to produce diketopiperazine (DKP) compounds such as albonoursin and cyclo(Phe-Leu). This study aimed to reveal the potential to synthesize diverse nonribosomal peptide and polyketide compounds as the other secondary metabolites different from DKP after clarifying the taxonomic position. Strain N11-50 was identified as Streptomyces albus, as it showed 100% 16S rRNA gene sequence similarities and 95.5% DNA–DNA relatedness to S. albus NBRC 13014T. We annotated the nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) gene clusters in the genome. Consequently, five NRPS, one hybrid PKS/NRPS, five type-I PKS and one type-II PKS gene clusters were observed, of which we predicted the products through bioinformatic analysis. These gene clusters were well conserved in already whole-genome sequence (WGS)-published strains belonging to S. albus. On the other hand, our taxonogenomic analysis revealed that three WGS-published S. albus strains were not S. albus. Two of the three should be classified as Streptomyces albidoflavus, and the remaining one was likely a new genomospecies. After reclassifying these appropriately, we demonstrated species-specific profiles of the NRPS and PKS gene clusters with little strain-level diversities. Full article
Show Figures

Figure 1

Back to TopTop