Antibiotic resistance has become one of the most serious threats to human health in recent years. In response to the increasing microbial resistance to the antibiotics currently available, it is imperative to develop new antibiotics or explore new approaches to combat antibiotic resistance. Antimicrobial peptides (AMPs) have shown considerable promise in this regard, as the microbes develop low or no resistance against them. The discovery and development of AMPs still confront numerous obstacles such as finding a target, developing assays, and identifying hits and leads, which are time-consuming processes, making it difficult to reach the market. However, with the advent of genome mining, new antibiotics could be discovered efficiently using tools such as BAGEL, antiSMASH, RODEO, etc., providing hope for better treatment of diseases in the future. Computational methods used in genome mining automatically detect and annotate biosynthetic gene clusters in genomic data, making it a useful tool in natural product discovery. This review aims to shed light on the history, diversity, and mechanisms of action of AMPs and the data on new AMPs identified by traditional as well as genome mining strategies. It further substantiates the various phases of clinical trials for some AMPs, as well as an overview of genome mining databases and tools built expressly for AMP discovery. In light of the recent advancements, it is evident that targeted genome mining stands as a beacon of hope, offering immense potential to expedite the discovery of novel antimicrobials.

Microbial bioaugmentation of coal is considered as a viable and ecologically sustainable approach for the utilization of low-rank coals (LRC). The search for novel techniques to derive high-value products from LRC is currently of great importance. In response to this demand, endeavors have been undertaken to develop microbially based coal solubilization and degradation techniques. The impact of supplementing activated sludge (AS) as a microbial augmentation to enhance LRC biodegradation was investigated in this study. The LRC and their biodegradation products were characterized using the following methods: excitation-emission Matrices detected fluorophores at specific wavelength positions (O, E, and K peaks), revealing the presence of organic complexes with humic properties. FTIR indicated the increased amount of carboxyl groups in the bioaugmented coals, likely due to aerobic oxidation of peripheral non-aromatic structural components of coal. The bacterial communities of LRC samples are primarily composed of Actinobacteria (up to 36.2%) and Proteobacteria (up to 25.8%), whereas the Firmicutes (63.04%) was the most abundant phylum for AS. The community-level physiological profile analysis showed that the microbial community AS had high metabolic activity of compared to those of coal. Overall, the results demonstrated successful stimulation of LRC transformation through supplementation of exogenous microflora in the form of AS.

Actinobacteria are renowned for their prolific production of diverse bioactive secondary metabolites. In recent years, there has been an increasing focus on exploring \"rare\" genera within this phylum for biodiscovery purposes, notably the Nocardiopsis genus, which will be the subject of the present study. Recognizing the absence of articles describing the research process of finding bioactive molecules from the genus Nocardiopsis in North African environments. We, therefore, present a historical overview of the discoveries of bioactive molecules of the genus Nocardiopsis originating from the region, highlighting their biological activities and associated reported molecules, providing a snapshot of the current state of the field, and offering insights into future opportunities and challenges for drug discovery. Additionally, we present a genome mining analysis of three genomes deposited in public databases that have been reported to be bioactive. A total of 36 biosynthetic gene clusters (BGCs) were identified, including those known to encode bioactive molecules. Notably, a substantial portion of the BGCs showed little to no similarity to those previously described, suggesting the possibility that the analyzed strains could be potential producers of new compounds. Further research on these genomes is essential to fully uncovering their biotechnological potential. Moving forward, we discuss the experimental designs adopted in the reported studies, as well as new avenues to guide the exploration of the Nocardiopsis genus in North Africa.

Sigma factors are transcriptional regulators that are part of complex regulatory networks for major cellular processes, as well as for growth phase-dependent regulation and stress response. Actinoplanes sp. SE50/110 is the natural producer of acarbose, an α-glucosidase inhibitor that is used in diabetes type 2 treatment. Acarbose biosynthesis is dependent on growth, making sigma factor engineering a promising tool for metabolic engineering. ACSP50_0507 is a homolog of the developmental and osmotic-stress-regulating Streptomyces coelicolor σHSc. Therefore, the protein encoded by ACSP50_0507 was named σHAs. Here, an Actinoplanes sp. SE50/110 expression strain for the alternative sigma factor gene ACSP50_0507 (sigHAs) achieved a two-fold increased acarbose yield with acarbose production extending into the stationary growth phase. Transcriptome sequencing revealed upregulation of acarbose biosynthesis genes during growth and at the late stationary growth phase. Genes that are transcriptionally activated by σHAs frequently code for secreted or membrane-associated proteins. This is also mirrored by the severely affected cell morphology, with hyperbranching, deformed and compartmentalized hyphae. The dehydrated cell morphology and upregulation of further genes point to a putative involvement in osmotic stress response, similar to its S. coelicolor homolog. The DNA-binding motif of σHAs was determined based on transcriptome sequencing data and shows high motif similarity to that of its homolog. The motif was confirmed by in vitro binding of recombinantly expressed σHAs to the upstream sequence of a strongly upregulated gene. Autoregulation of σHAs was observed, and binding to its own gene promoter region was also confirmed.

Thermophilic actinomycetes are commonly found in extreme environments and can thrive and adapt to extreme conditions. These organisms exhibit substantial variation and garnered significant interest due to their remarkable enzymatic activities. This study evaluated the potential of Streptomyces griseorubens NBR14 and Nocardiopsis synnemataformans NBRM9 strains to produce thermo-stable amylase via submerged fermentation using wheat and bean straw. The Box-Behnken design was utilized to determine the optimum parameters for amylase biosynthesis. Subsequently, amylase underwent partial purification and characterization. Furthermore, the obtained hydrolysate was applied for ethanol fermentation using Saccharomyces cerevisiae. The optimal parameters for obtaining the highest amylase activity by NBR14 (7.72 U/mL) and NBRM9 (26.54 U/mL) strains were found to be 40 and 30 °C, pH values of 7, incubation time of 7 days, and substrate concentration (3 and 2 g/100 mL), respectively. The NBR14 and NBRM9 amylase were partially purified, resulting in specific activities of 251.15 and 144.84 U/mg, as well as purification factors of 3.91 and 2.69-fold, respectively. After partial purification, the amylase extracted from NBR14 and NBRM9 showed the highest activity level at pH values of 9 and 7 and temperatures of 50 and 60 °C, respectively. The findings also indicated that the maximum velocity (Vmax) for NBR14 and NBRM9 amylase were 57.80 and 59.88 U/mL, respectively, with Km constants of 1.39 and 1.479 mM. After 48 h, bioethanol was produced at concentrations of 5.95 mg/mL and 9.29 mg/mL from hydrolyzed wheat and bean straw, respectively, through fermentation with S. cerevisiae. Thermophilic actinomycetes and their α-amylase yield demonstrated promising potential for sustainable bio-ethanol production from agro-byproducts.

Zearalenone (ZEN) is a prevalent mycotoxin found in grains and grain-derived products, inducing adverse health effects in both animals and humans. The in-field application of microorganisms to degrade and detoxify ZEN is a promising strategy to enhance the safety of food and feed. In this study, we investigated the potential of three actinobacterial strains to degrade and detoxify ZEN in vitro and in planta on wheat ears. The residual ZEN concentration and toxicity in the samples were analysed with UHPLC-MS/MS and a bioluminescence BLYES assay, respectively. Streptomyces rimosus subsp. rimosus LMG19352 could completely degrade and detoxify 5 mg/L ZEN in LB broth within 24 h, along with significant reductions in ZEN concentration both in a minimal medium (MM) and on wheat ears. Additionally, it was the only strain that showed a significant colonisation of these ears. Rhodococcus sp. R25614 exhibited partial but significant degradation in LB broth and MM, whereas Streptomyces sp. LMG16995 degraded and detoxified ZEN in LB broth after 72 h by 39% and 33%, respectively. Although all three actinobacterial strains demonstrated the metabolic capability to degrade and detoxify ZEN in vitro, only S. rimosus subsp. rimosus LMG19352 showed promising potential to mitigate ZEN in planta. This distinction underscores the importance of incorporating in planta screening assays for assessing the potential of mycotoxin-biotransforming microorganisms as biocontrol agents.

Deep-sea environments, as relatively unexplored extremes within the Earth\'s biosphere, exhibit notable distinctions from terrestrial habitats. To thrive in these extreme conditions, deep-sea actinomycetes have evolved unique biochemical metabolisms and physiological capabilities to ensure their survival in this niche. In this study, five actinomycetes strains were isolated and identified from the Mariana Trench via the culture-dependent method and 16S rRNA sequencing approach. The antimicrobial activity of Microbacterium sp. B1075 was found to be the most potent, and therefore, it was selected as the target strain. Molecular networking analysis via the Global Natural Products Social Molecular Networking (GNPS) platform identified 25 flavonoid compounds as flavonoid secondary metabolites. Among these, genistein was purified and identified as a bioactive compound with significant antibacterial activity. The complete synthesis pathway for genistein was proposed within strain B1075 based on whole-genome sequencing data, with the key gene being CHS (encoding chalcone synthase). The expression of the gene CHS was significantly regulated by high hydrostatic pressure, with a consequent impact on the production of flavonoid compounds in strain B1075, revealing the relationship between actinomycetes\' synthesis of flavonoid-like secondary metabolites and their adaptation to high-pressure environments at the molecular level. These results not only expand our understanding of deep-sea microorganisms but also hold promise for providing valuable insights into the development of novel pharmaceuticals in the field of biopharmaceuticals.

Bioprospecting the secondary metabolism of underexplored Actinomycetota taxa is a prolific route to uncover novel chemistry. In this work, we report the isolation, structure elucidation, and bioactivity screening of cellulamides A and B (1 and 2), two novel linear peptides obtained from the culture of the macroalga-associated Cellulosimicrobium funkei CT-R177. The host of this microorganism, the Chlorophyta Codium tomentosum, was collected in the northern Portuguese coast and, in the scope of a bioprospecting study focused on its associated actinobacterial community, strain CT-R177 was isolated, taxonomically identified, and screened for the production of antimicrobial and anticancer compounds. Dereplication of a crude extract of this strain using LC-HRMS(/MS) analysis unveiled a putative novel natural product, cellulamide A (1), that was isolated following mass spectrometry-guided fractionation. An additional analog, cellulamide B (2) was obtained during the chromatographic process and chemically characterized. The chemical structures of the novel linear peptides, including their absolute configurations, were elucidated using a combination of HRMS, 1D/2D NMR spectroscopy, and Marfey\'s analysis. Cellulamide A (1) was subjected to a set of bioactivity screenings, but no significant biological activity was observed. The cellulamides represent the first family of natural products reported from the Actinomycetota genus Cellulosimicrobium, showcasing not only the potential of less-explored taxa but also of host-associated marine strains for novel chemistry discovery.

Type 1 polyketides are a major class of natural products used as antiviral, antibiotic, antifungal, antiparasitic, immunosuppressive, and antitumor drugs. Analysis of public microbial genomes leads to the discovery of over sixty thousand type 1 polyketide gene clusters. However, the molecular products of only about a hundred of these clusters are characterized, leaving most metabolites unknown. Characterizing polyketides relies on bioactivity-guided purification, which is expensive and time-consuming. To address this, we present Seq2PKS, a machine learning algorithm that predicts chemical structures derived from Type 1 polyketide synthases. Seq2PKS predicts numerous putative structures for each gene cluster to enhance accuracy. The correct structure is identified using a variable mass spectral database search. Benchmarks show that Seq2PKS outperforms existing methods. Applying Seq2PKS to Actinobacteria datasets, we discover biosynthetic gene clusters for monazomycin, oasomycin A, and 2-aminobenzamide-actiphenol.

Microalgae growth-promoting bacteria (MGPB), both actinobacteria and non-actinobacteria, have received considerable attention recently because of their potential to develop microalgae-bacteria co-culture strategies for improved efficiency and sustainability of the water-energy-environment nexus. Owing to their diverse metabolic pathways and ability to adapt to diverse conditions, microalgal-MGPB co-cultures could be promising biological systems under uncertain environmental and nutrient conditions. This review proposes the recent updates and progress on MGPB for microalgae cultivation through co-culture strategies. Firstly, potential MGPB strains for microalgae cultivation are introduced. Following, microalgal-MGPB interaction mechanisms and applications of their co-cultures for biomass production and wastewater treatment are reviewed. Moreover, state-of-the-art studies on synthetic biology and metabolic network analysis, along with the challenges and prospects of opting these approaches for microalgal-MGPB co-cultures are presented. It is anticipated that these strategies may significantly improve the sustainability of microalgal-MGPB co-cultures for wastewater treatment, biomass valorization, and bioproducts synthesis in a circular bioeconomy paradigm.