While the Zygomycete fungus Conidiobolus coronatus primarily infects insects, it can be pathogenic to mammals as well, including humans. High variability in the treatment of this fungal infection with currently available drugs, including azole drugs is a very common phenomenon. Azoles bind to the cytochrome P450 monooxygenases (P450s/CYP) including CYP51, a sterol 14-α-demethylase, inhibiting the synthesis of cell membrane ergosterol and thus leading to the elimination of infecting fungi. Despite P450’s role as a drug target, to date, no information on C. coronatus P450s has been reported. Genome-wide data mining has revealed the presence of 142 P450s grouped into 12 families and 21 subfamilies in C. coronatus. Except for CYP51, the remaining 11 P450 families are new (CYP5854-CYP5864). Despite having a large number of P450s among entomopathogenic fungi, C. coronatus has the lowest number of P450 families, which suggests blooming P450s. Further analysis has revealed that 79% of the same family P450s is tandemly positioned, suggesting that P450 tandem duplication led to the blooming of P450s. The results of this study; i.e., unravelling the C. coronatus P450 content, will certainly help in designing experiments to understand P450s’ role in C. coronatus physiology, including a highly variable response to azole drugs with respect to P450s.

Background Endophytes, especially those that are found from ethnopharmacologically noteworthy medicinal plants have attracted attention due to their diverse bioactive metabolites of pharmacological importance. Methods This study aimed at isolating endophytic bacterium from the leaves of Anredera cordifolia CIX1 for its bioactive metabolites. The endophytic isolates were identified by 16S rRNA sequence and investigated for antibiotic sensitivity using different antibiotics. The secondary metabolites were evaluated for antibacterial activity against four bacterial strains. The 2-diphenyl-1-picrylhydrazyl (DPPH) and 2, 2′-azinobis (3- ethylbenzothiazoline-6-sulfonic acid) (ABTS) methods were used to assess their scavenging activities. The chemical components were analysed by gas chromatography-mass spectrometry (GC-MS). Results Out of 13 isolates, Isolate 1 was identified as Pseudomonas aeruginosa CP043328.1. It was resistant to clindamycin, ertapenem, penicillin G, amoxicillin, cephalothin and kanamycin but sensitive to imipenem, meropenem, and gentamycin. Its extract demonstrated antibacterial activity with minimum inhibitory concentration value of 0.098 against Bacillus cereus (ATCC 10102) and Staphylococcus aureus (ATCC 25925) and 0.391 mg/ml against Escherichia coli (ATCC 25922) and Proteus mirabilis (ATCC 25933). The extract revealed DPPH and ABTS scavenging activities with half maximal inhibitory concentration value of 0.650 mg/ml and 0.15 mg/ml, respectively. The GC-MS revealed a total of 15 compounds with diisooctyl phthalate (50.51%) and [1, 2, 4] oxadiazole, 5-benzyl-3 (10.44%) as major components. Conclusions P. aeruginosa CP043328.1 produced secondary metabolites with antibacterial and antioxidant activities.

Encephalartos ferox is cycad belonging to the Zamiaceae family. It is endemic in northern Kwazulu-Natal, South Africa. 12 The plant parts, especially the leaves are used as prophylaxis in the treatment of oestrogen-dependent tumour and diabetes. 13 However, there are limited studies reporting on the medicinal properties of its fruit. Our previous study investigated the chemical composition of the E. ferox methanolic fruit extract. The gas chromatography mass spectrophotometry chromatogram profile revealed a total of eight volatile compounds namely cis-Vaccenic acid (1), 9-Octadecenoic acid, 1,2,3-propanetriyl ester (2), 4H-Pyran-4-one, 2,3-dihydro-3,5-dihydroxy (3), 9-Hexadecenoic acid (4) and Pentadecanoic acid (5). Other compounds were 10-Octadecenoic acid, methyl ester (6), Hexadecanoic acid, 2-hydroxy-1-(hydroxym) (7) and 11, 14-Eicosadienoic acid, methyl ester (8). These compounds have been recognised to possess ABSTRACT Background: Plant based products are recognised as sources of drugs for treatment of diseases. Objective: The study aimed at predicting the physicochemical, pharmacokinetics, drug-likeness and toxicity of the compounds identified from the methanolic Encephalartos ferox fruit extract. Methods: The physicochemical, pharmacokinetics properties and bioactive scores of the compounds were predicted using SwissADME and Molinspiration computational tools. Drug-likeness of the compounds was evaluated based on the Lipinski rule of five (Ro5). In silico mutagenicity, carcinogenicity and inhibition of human ether-ago go related (hERG) gene were also investigated using PreADMET web tool. Results: The physicochemical properties showed the compounds, except 9-Octadecenoic acid, 1, 2, 3-propanetriyl ester to adhere to Ro5. The evaluation of their inhibitory effects profile in several cytochrome P450 isoforms indicate that all the compounds are not the inhibitors of CYP2C19 and CYP3A4 whereas some inhibited CYP1A2, CYP2C9 and CYP2D6. The drug-likeness evaluation employed Ro5 as a filter and all compounds complied with it except for 9-Octadecenoic acid, 1, 2, 3-propanetriyl ester. About 50% of the tested compound were found to be safe as they did not exhibit antimutagenic and carcinogenic effects. Moreover, the risk of inhibition of hERG gene revealed to be low to medium risk depending on the compound. Conclusion: The calculated physicochemical and pharmacokinetic properties suggest that most of the compounds are safe and have promising oral bioavailability.

The constant increase in drug resistance, occurrence of incurable diseases and high medical costs, have necessitated bio-prospecting of fungi as alternative sources of therapeutic compounds. This study aimed at assessing the antibacterial effect and mode of action of secondary metabolites from fungal endophyte associated with Aloe ferox Mill. Endophytic fungus was isolated from the gel of A. ferox and identified by internal transcribed spacer (ITS) rRNA gene sequence analysis. The targets of antibacterial activity were assessed based on minimum inhibitory concentration (MIC) and the effect of the extract on respiratory chain dehydrogenase (RCD) and membrane integrity. Fourier transform-infrared spectrophotometer (FTIR) was employed to ascertain functional groups. The fungus with the most promising antibiotic-production was identified as Aspergillus welwitschiae MK450668.1. Its extract exhibited antibacterial activity with the MIC values of 0.5 and 1 mg/mL against Staphylococcus aureus (ATCC 25925) and Escherichia coli (ATCC 25922). It demonstrated the inhibitory effect on the RCD activity and destruction of membrane integrity on the test bacteria. FTIR spectrum revealed hydroxyl, amine and alkene groups. A. welwitschiae MK450668.1 serves as a potential source of effective compounds to combat the challenge of drug resistance.

Background The emergence of drug resistance among pathogens has resulted in renewed interest in bioprospecting for natural microbial products. Methods This study aimed to bioprospecting endophytic actinobacterium associated with Aloe ferox Mill for its antibacterial activity. Endophytic actinomycetes were isolated from the gel of A. ferox Mill by surface sterilization technique using actinomycete isolation agar. The isolate with a promising antibacterial activity was identified using 16S rRNA sequence analysis. The minimum inhibitory concentration (MIC) of the extract was assessed by the micro-dilution method and its effect on the respiratory chain dehydrogenase (RCD) activity was ascertained by the iodonitrotetrazolium chloride (INT) assay. Fourier transform-infrared spectrophotometer (FTIR) and gas chromatography-mass spectrophotometry (GC-MS) were employed to identify functional groups and the chemical constituents, respectively. Results The actinobacterium was found to be Streptomyces olivaceus CP016795.1. Its extract displayed noteworthy antibacterial activity (MIC ≤1 mg/mL) against Staphylococcus aureus (ATCC 25925), Bacillus cereus (ATCC 10102), and Escherichia coli (ATCC 25922); and showed an inhibitory effect on the RCD activity. FTIR spectrum displayed hydroxyl, amine, and aromatic groups, and the GC–MS revealed 5-Hydroxymethylfurfural as the main constituent (19.47%). Conclusions S. olivaceus CP016795.1 can serve as a potential source of effective antibacterial compounds.