Microbial lipids, also known as single-cell oils (SCOs), are highly attractive feedstocks for biodiesel production due to their fast production rates, minimal labor requirements, independence from seasonal and climatic changes, and ease of scale-up for industrial processing. Among the SCO producers, the less explored filamentous fungi (molds) exhibit desirable features such as a repertoire of hydrolyzing enzymes and a unique pellet morphology that facilitates downstream harvesting. Although several oleaginous filamentous fungi have been identified and explored for SCO production, high production costs and technical difficulties still make the process less attractive compared to conventional lipid sources for biodiesel production. This review aims to highlight the ability of filamentous fungi to hydrolyze various organic wastes for SCO production and explore current strategies to enhance the efficiency and cost-effectiveness of the SCO production and recovery process. The review also highlights the mechanisms and components governing lipogenic pathways, which can inform the rational designs of processing conditions and metabolic engineering efforts for increasing the quality and accumulation of lipids in filamentous fungi. Furthermore, we describe other process integration strategies such as the co-production with hydrogen using advanced fermentation processes as a step toward a biorefinery process. These innovative approaches allow for integrating upstream and downstream processing units, thus resulting in an efficient and cost-effective method of simultaneous SCO production and utilization for biodiesel production.

The discovery of silent biosynthetic gene clusters (BGCs) in fungi provides unlimited prospects to harness the secondary metabolites encoded by gene clusters for various applications, including pharmaceuticals. Amplifying these prospects is the new interest in exploring fungi living in the extremes, such as those associated with plants (fungal endophytes). Fungal species in endosymbiosis relationship with plants are recognized as the future factories of clinically relevant agents since discovering that they can produce similar metabolites as their plant host. The endophytes produce these compounds in natural environments as a defense mechanism against pathogens that infect the plant host or as a strategy for mitigating competitors. The signaling cascades leading to the expression of silent biosynthetic gene clusters in the natural environment remain unknown. Lack of knowledge on regulatory circuits of biosynthetic gene clusters limits the ability to exploit them in the laboratory. They are often silent and require tailor-designed strategies for activation. Epigenetic modification using small molecular compounds that alter the chromatin network, leading to the changes in secondary metabolites profile, has achieved considerable success. This review aims to comprehensively analyze the secondary metabolite profiles expressed after treatment with various epigenetic modifiers. We first describe the regulatory circuits governing the expression of secondary metabolites in fungi. Following this, we provide a detailed review of the small molecular modifiers, their mechanism(s) of action, and the diverse chemistries resulting from epigenetic modification. We further show that genetic deletion or epigenetic inhibition of histone deacetylases does not always lead to the overexpression or induction of silent secondary metabolites. Instead, the response is more complex and often leads to differential expression of secondary metabolites. Finally, we propose using this strategy as an initial screening tool to dereplicate promising fungal species.

The increasing reports of multidrug-resistant Klebsiella pneumoniae have emerged as a public health concern, raising questions about the potential routes for the evolution and dissemination of the pathogenic K. pneumoniae into environmental reservoirs. Potential drivers of the increased incidence of antimicrobial-resistant environmental K. pneumoniae include the eminent global climatic variations as a direct or indirect effect of human activities. The ability of microorganisms to adapt and grow at an exponential rate facilitates the distribution of environmental strains with acquired resistant mutations into water systems, vegetation, and soil which are major intersection points with animals and humans. The bacterial pathogen, K. pneumoniae, is one of the critical-priority pathogens listed by the World Health Organization, mostly associated with hospital-acquired infections. However, the increasing prevalence of pathogenic environmental strains with similar characteristics to clinical-antibiotic-resistant K. pneumoniae isolates is concerning. Considering the eminent impact of global climatic variations in the spread and dissemination of multidrug-resistant bacteria, in this review, we closely assess factors influencing the dissemination of this pathogen resulting in increased interaction with the environment, human beings, and animals. We also look at the recent developments in rapid detection techniques as part of the response measures to improve surveillance and preparedness for potential outbreaks. Furthermore, we discuss alternative treatment strategies that include secondary metabolites such as biosurfactants and plant extracts with high antimicrobial properties.

The continuous burden of human immunodeficiency virus-1 in Sub-Saharan Africa, coupled with the inability of antiretroviral agents to eradicate HIV-1 from viral reservoirs, the potential risks of drug resistance development, and the development of adverse effects, emphasizes the need to develop a new class of HIV-1 inhibitors. Here, we cultivated four endophytic fungal isolates from a medicinal plant, Albizia adianthifolia with the addition of small epigenetic modifiers, sodium butyrate, and valproic acid, to induce the expression of biosynthetic gene clusters encoding active secondary metabolites with probable anti-HIV activities. We identified a non-toxic crude extract of the endophytic fungus Penicillium chrysogenum treated with sodium butyrate to possess significantly greater anti-HIV activity than the untreated extracts. Penicillium chrysogenum P03MB2 showed anti-HIV activity with an IC₅₀ of 0.6024 µg/mL compared to untreated fungal crude extract (IC₅₀ 5.053 µg/mL) when treated with sodium butyrate. The profile of secondary metabolite compounds from the bioactive, partially purified extracts were identified by gas chromatography-mass spectrometry (GC-MS), and more bioactive compounds were detected in treated P. chrysogenum P03MB2 fractions than in untreated fractions. Pyrrolo[1,2-a]pyrazine-1,4-dione, hexahydro (13.64%), cyclotrisiloxane, hexamethyl (8.18%), cyclotetrasiloxane, octamethyl (7.23%), cyclopentasiloxane, decamethyl (6.36%), quinoline, 1,2-dihydro-2,24-trimethyl (5.45%), propanenitrile (4.55%), deca-6,9-diene (4.55%), dibutyl phthalate (4.55%), and silane[1,1-dimethyl-2-propenyl)oxy]dimethyl (2.73%) were the most abundant compounds. These results indicate that treatment of endophytic fungi with small epigenetic modifiers enhances the secretion of secondary metabolites with stronger anti-HIV-1 properties, acknowledging the feasibility of epigenetic modification as an innovative approach for the discovery of cryptic fungal metabolites which can be developed into therapeutic compounds.

Antiretroviral treatment has significantly reduced human immunodeficiency virus infection and mortality. However, the current treatment regimen is limited by adverse side effects, the emergence of drug resistance, and the inability to eliminate viral reservoirs. Here, fifteen endophytic fungi were isolated from Sclerocarya birrea and Hypoxis plants. Crude extracts of Alternaria alternata (strain ID PO4PR1, PO4PR2, and PO2PL1) of the fifteen isolate’s crude extracts showed anti-HIV-1 activity in TZM-bl cell line at inhibitory concentration (IC₅₀) values ranging from 0.017 to 1.170 μg/ml. The three crude extracts also maintained the virus replication inhibition profile on PBMCs and CD4⁺ T cells at concentrations ranging from 0.3 to 50.2 ng/ml. Partial purification using the solid phase extraction and analysis with Gas Chromatography-Mass spectrophotometry showed a diverse profile. The bioactive compounds were identified based on peak area, retention time, similarity index. The major compounds from GC-MS analysis of A. Alternata revealed the existence of cyclotrisiloxane octamethyl (22.92%); Propaninitrile (16,67%); Pyrrolol[1,2-a]pyrazine-1,4-dione, hexahydro-3-(2-methyl propyl) (10.42%); Silane, diethylethoxy(2-ethoxyethyloxy) (4.17%); Coumarin, 3,4-dihydro-4,5,7-trimethyl- 4,5,7-Trimethyl-2-chromanone (13.7%) and 1,2-Cyclobutanedicarbonitrile (2.08%) with previously reported biological activities such as antimicrobial, anti-inflammatory and antioxidant properties. Therefore, these bioactive compounds from A. alternata fungal endophytes could be repurposed as potential anti-HIV agents. This study showed the potential of endophytic fungi, Alternaria alternata from S. birrea, and Hypoxis species as producers of anti-HIV compounds.