A comprehensive review of biosurfactant production and its uses in the pharmaceutical industry.

Biosurfactants are naturally occurring, surface-active chemicals generated by microorganisms and have attracted interest recently because of their numerous industrial uses. Compared to their chemical equivalents, they exhibit qualities that include lower toxic levels, increased biodegradable properties, and unique physiochemical properties. Due to these traits, biosurfactants have become attractive substitutes for synthetic surfactants in the pharmaceutical industry. In-depth research has been done in the last few decades, demonstrating their vast use in various industries. This review article includes a thorough description of the various types of biosurfactants and their production processes. The production process discussed here is from oil-contaminated waste, agro-industrial waste, dairy, and sugar industry waste, and also how biosurfactants can be produced from animal fat. Various purification methods such as ultrafiltration, liquid-liquid extraction, acid precipitation, foam fraction, and adsorption are required to acquire a purified product, which is necessary in the pharmaceutical industry, are also discussed here. Alternative ways for large-scale production of biosurfactants using different statistical experimental designs such as CCD, ANN, and RSM are described here. Several uses of biosurfactants, including drug delivery systems, antibacterial and antifungal agents, wound healing, and cancer therapy, are discussed. Additionally, in this review, the future challenges and aspects of biosurfactant utilization in the pharmaceutical industry and how to overcome them are also discussed.

Extraction and characterization of carotenoid pigments with antioxidant and antibacterial potential from marine yeast Rhodotorula sp. KSB1.

Pigments are coloring agents used widely in different industrial sectors. There is a demand for using natural pigments rather than synthetic dyes because of the health hazards caused by synthetic dyes. Many natural pigments have different medicinal activities which can contribute to the nutritional value of the product. This study was carried forward with marine yeasts which can produce pigments. A total of 4 marine yeast isolates were recovered from the mangrove area of Sundarbans, West Bengal, India. Among them, the isolate KSB1 produced 856 µg/g total concentration of carotenoid pigment and the dry mass weight was 3.56 g/L. The stability of the extracted pigments was checked using temperature, pH, UV light exposure time, and different saline conditions. The pigments were characterized using HPLC and FTIR analysis. All of the extracted pigments showed good antioxidant activity in DPPH, metal chelating, and reducing power assay. The pigments were also found to have good antibacterial activity against the bacterial pathogens Staphylococcus aureus, Listeria monocytogenes, and Escherichia coli. Carotenoid pigment from KSB1 was found to have maximum activity in all the pathogens. The cytogenotoxicity using onion roots and phytotoxicity analysis indicated that the pigments were non-toxic and safe for cells. Finally, the potential marine yeast was identified using 18 s rRNA sequencing and identified as Rhodotorula sp. KSB1 (Accession no. MH782232).

EPS-mediated biosynthesis of nanoparticles by Bacillus stratosphericus A07, their characterization and potential application in azo dye degradation.

Microbial exopolysaccharides (EPS) are biocompatible, biodegradable, and less toxic substances secreted outside the cell. They adsorb metal cations to its surface, making it another captivating property, which helps in stabilizing and biosynthesizing metal nanoparticles. Owing to these properties, we adopted bacterial EPS toward the green synthesis of nanoparticles and its application in the removal of azo dyes. Extracted EPS weighed 2.6 mg/mL from the most potential isolate A07 with 385 µg/mg of the carbohydrate content. The top three isolates were subjected to nanoparticle synthesis via the intracellular method and, by their extracted EPS, silver nanoparticles (AgNP) with the size around 87 nm were successfully produced by both methods mediated by the most potent isolate. The nanoparticles were characterized by UV-Vis spectroscopy, X-ray diffraction studies, atomic force microscopy, and FT-IR analysis. The nanoparticles were employed for dye degradation of azo dyes, namely, Methyl Orange (MO) and Congo Red (CO). EPS-Ag NPs showed fair degradation capability determined by UV-Vis kinetic studies. The work suggests electron transfer from reducing agent to dye molecule mediated by nanoparticles, destroying the dye chromophore. This makes EPS-Ag NPs a suitable, cheap, and environment-friendly candidate for biodegradation of harmful azo dyes. The most potential isolate was identified as Bacillus stratosphericus by 16S rRNA sequencing and submitted to GenBank under the accession id MK968439.

A study on the utility of immobilized cells of indigenous bacteria for biodegradation of reactive azo dyes.

Azo dyes are recalcitrant compounds used as a colorant in various industries. The pollution caused by their extensive usage has adversely affected the environment for years. The existing physicochemical methods for dye pollution remediation are rather inefficient and hence there is a dearth of low-cost, potential systems capable of dye degradation. The current research studies the biodegradation potential of immobilized bacterial cells against azo dyes Reactive Orange 16 (RO-16) and Reactive Blue 250 (RB-250). Two indigenous dye degrading bacteria Bacillus sp. VITAKB20 and Lysinibacillus sp. KPB6 was isolated from textile sludge sample. Free cells of Bacillus. sp. VITAKB20 degraded 92.38% of RO-16 and that of Lysinibacillus sp. KPB6 degraded 95.36% of RB-250 within 72 h under static conditions. Upon immobilization with calcium alginate, dye degradation occurred rapidly. Bacillus. sp. VITAKB20 degraded 97.5% of RO-16 and Lysinibacillus sp. KPB6 degraded 98.2% of RB-250 within 48 h under shaking conditions. Further, the nature of dye decolorization was biodegradation as evident by high-performance liquid chromatography (HPLC), and Fourier-transform infrared spectroscopy (FTIR) results. Phytotoxicity and biotoxicity assays revealed that the degraded dye products were less toxic in nature than the pure dyes. Thus, immobilization proved to be a highly likely alternative treatment for dye removal.

An ex-situ and in vitro approach towards the bioremediation of carcinogenic hexavalent chromium.

Chromium, ranking the second most among toxic heavy metal pollutants in the world, causing respiratory, cardiovascular and renal problems in human beings is under study herein. We examined the biological remediation of the carcinogenic Cr (VI) polluted soils by indigenous yeast isolates. The total element analysis of the treated sample was determined by Energy Dispersion X-ray Micro Analysis (EDXMA). The sample under study was observed to have a high concentration of 458.29 mgKg-1 Cr (VI), determined by Atomic Absorption Spectroscopy (AAS) and DPC analysis. The most tolerant isolate designated as CSR was used for in vitro and ex-situ bioremediation studies of Cr (VI). The isolate achieved significant bioremediation of 86% in vitro and 75.12% in ex-situ method. The optimal conditions for in vitro bioremediation were found to be 28 °C and a pH of 6. The ITS1, 5.8S rRNA and D1, D2 domain of LSU rRNA gene characterization of the isolate CSR illustrated that it belongs to Ustilago genera. The isolate was deposited in NCBI GenBank as Ustilago sp. CSR (KY284846). Although, Ustilago is generally a pathogenic fungus, our study opens up the scope of using Ustilago spp. for bioremediation of the carcinogenic heavy metal Chromium.

Fatty acyl compounds from marine Streptomyces griseoincarnatus strain HK12 against two major bio-film forming nosocomial pathogens; an in vitro and in silico approach.

The perpetual increase in the resistance offered by biofilm-forming nosocomial pathogens has become a critical clinical challenge. Marine Streptomyces sps present a promising future of novel compounds with novel applications. We focus on the anti-biofilm activity of marine Streptomyces against two major nosocomial pathogens from clinical samples, Pseudomonas aeruginosa and Staphylococcus aureus. Herein, Streptomyces griseoincarnatus, a species known to harbour alkaline protease inhibitors and anti-tumour compounds were found to exhibit anti-biofilm activity. The study progresses to decipher the anti-biofilm potential of the extract as 82.657 ±â€¯1.1002% against P. aeruginosa and 78.973 ±â€¯1.672% against S. aureus at 100 µg/mL. The strain under study, S. griseoincarnatus HK 12 (accession no MF100857) has revealed the presence of certain fatty acyl compounds namely, 13Z-Octadecenal, 9Z-Octadecenal, Arachidic acid, Tetracosanoic acid and Erucic acid by GC-MS screening. Furthermore, the active compounds were docked against the quorum sensing system, LasI. The compound 13Z-Octadecenal was found to bind to the conserved sites of substrate binding with a binding energy of -1.90 kcal/mol thus, affirming the inhibitory activity of the fatty acyl compound. These active compounds were previously reported to be a part of active extracts exhibiting relevant antagonistic activities, but this so far is the first time they are found possessing anti-biofilm activity. Interestingly, the toxicity level of the extract at a high concentration of 500 µg/mL is as low as 11.5% when tested against human lung cancer lines, A549. Thus the report highlights the evidence of the potential of S griseoincarnatus HK12 to be an active and safe anti-biofilm agent.

Aerobic biodegradation of azo dye Acid Black-24 by Bacillus halodurans.

Bacillus halodurans MTCC 865 was employed for decolorization of textile azo dye, Acid Black-24 (AB-24). Thousand mgl⁻¹ of AB-24 was decolorized with 90% efficiency by the strain within 6 hrs at pH 9 and 37 °C with 5% NaCl under static conditions in screening medium. Decolorization was evaluated by measuring the periodic decrease in absorbance at 557 nm (λ(max)). Biodegradation of Acid Black-24 was determined by FTIR and HPLC. The FTIR spectrum of the AB-24 dye suggests the presence of azo bond (-N = N-) peak at 1618.28 cm⁻¹. Absence of the azo bond in the degraded sample spectrum indicates biodegradation of the dye. Formation of metabolites with different retention times in HPLC analysis further confirmed degradation of the azo dye, Acid Black-24 by Bacillus halodurans.

Pharmacokinetic studies, molecular docking, and molecular dynamics simulations of phytochemicals from Morus alba: a multi receptor approach for potential therapeutic agents in colorectal cancer.

This study explores the therapeutic potential of phytochemicals derived from Morus alba for colorectal cancer (CRC) treatment. Colorectal cancer is a global health concern with increasing mortality rates, necessitating innovative strategies for prevention and therapy. Employing in silico analysis, molecular docking techniques (MDT), and molecular dynamics simulations (MDS), the study investigates the interactions between Morus alba-derived phytochemicals and key proteins (AKT1, Src, STAT3, EGFR) implicated in CRC progression. ADME/T analysis screens 78 phytochemicals for drug-like and pharmacokinetic properties. The study integrates Lipinski's Rule of Five and comprehensive bioactivity assessments, providing a nuanced understanding of Morus alba phytoconstituent's potential as CRC therapeutic agents. Notably, 14 phytochemicals out of 78 emerge as potential candidates, demonstrating oral bioavailability and favorable bioactivity scores. Autodock 1.5.7 is employed for energy minimization followed by molecular docking with the highest binding energy observed to be - 11.7 kcal/mol exhibited by Kuwanon A against AKT1. Molecular dynamics simulations and trajectory path analysis were conducted between Kuwanon A and AKT1 at the Pleckstrin homology (PH) domain region (TRP80), revealing minimal deviations. In comparison to the standard drug Capivasertib, the phytochemical Kuwanon A emerges as a standout candidate based on computational analysis. This suggests its potential as an alternative to mitigate the limitations associated with the standard drug. The research aims to provide insights for future experimental validations and to stimulate the development of Kuwanon A as a novel, effective therapeutic agent for managing colorectal cancer.

Aerobic biodegradation of Azo dye by Bacillus cohnii MTCC 3616; an obligately alkaliphilic bacterium and toxicity evaluation of metabolites by different bioassay systems.

An obligate alkaliphilic bacterium Bacillus cohnii MTCC 3616 aerobically decolorized a textile azo dye Direct Red-22 (5,000 mg l⁻¹) with 95 % efficiency at 37 °C and pH 9 in 4 h under static conditions. The decolorization of Direct Red-22 (DR-22) was possible through a broad pH (7-11), temperature (10-45 °C), salinity (1-7 %), and dye concentration (5-10 g l⁻¹) range. Decolorization of dye was assessed by UV-vis spectrophotometer with reduction of peak intensity at 549 nm (λ(max)). Biodegradation of dye was analyzed by Fourier transform infrared spectroscopy (FTIR) and high-performance liquid chromatography (HPLC). The FTIR spectrum revealed that B. cohnii specifically targeted azo bond (N=N) at 1,614.42 cm⁻¹ to break down Direct Red-22. Formation of metabolites with different retention times in HPLC analysis further confirmed the degradation of dye. The phytotoxicity test with 5,000 mg l⁻¹ of untreated dye showed 80 % germination inhibition in Vigna mungo, 70 % in Sorghum bicolor and 80 % in Vigna radiata. No germination inhibition was noticed in all three plants by DR-22 metabolites at 5,000 mg l⁻¹. Biotoxicity test with Artemia salina proved the lethality of the azo dye at LC50 of 4 and 8 % for degraded metabolites by causing death of its nauplii compared to its less toxic-degraded metabolites. Bioaccumulation of dye was observed in the mid-gut of A. salina. The cytogenotoxicity assay on the meristematic root tip cells of Allium cepa further confirmed the cytotoxic nature of azo dye (DR-22) with decrease in mitotic index (0.5 % at 500 ppm) and increase in aberrant index (4.56 %) over 4-h exposure period. Genotoxic damages (lagging chromosome, metaphase cluster, chromosome bridges, and dye accumulation in cytoplasm) were noticed at different stages of cell cycle. The degraded metabolites had negligible cytotoxic and genotoxic effects.

Marine actinobacterial mediated gold nanoparticles synthesis and their antimalarial activity.

Streptomyces sp LK-3 (JF710608) mediated Gold nanoparticles (Au-N-LK3) were found within the size range of 5-50 nm. Au-N-LK3 treatment in Plasmodium berghei ANKA (PbA) infected mice delayed the parasitemia rise (~6%) compared to PbA infection on 8 days post infection. Survivability of mice increases to ~85% in Au-N-LK3 treated mice in contrast to in PbA (~50%) infected mice in 8 dpi with respect to control. During Au-N-LK3 treatment in PbA infection, histomorphological analysis revealed as such no change in spleen and liver tissue during 8 dpi. Our results confirmed up-regulation of TGF-ß and down-regulation of TNF-α in tissue and serum level in PbA infected Au-N-LK3 treated mice compared to PbA infection. No significant changes were found in the hatchability of Artemia embryos upto 8 mg. The results obtained suggest that the Au-N-LK3 possess anti-malarial activity and could be considered as a potential source for anti-malarial drug development. FROM THE CLINICAL EDITOR: These investigators present a method of marine actinobacteria mediated synthesis of gold nanoparticles, resulting in nanoparticles that possess anti-malarial activity and could be considered in future anti-malarial drug development.

Protease inhibitors as a potential agent against visceral Leishmaniasis: A review to inspire future study.

Leishmaniasis is transmitted by sandfly which carries the intracellular protozoa in their midgut. Among visceral, cutaneous and mucocutaneous leishmaniasis, visceral type that is caused by Leishmania donovani is the most lethal one. Findings of leishmanial structure and species took place in 19th century and was initiated by Donovan. Leishmaniasis is still a major concern of health issues in many endemic countries in Asia, Africa, the Americas, and the Mediterranean region. Worldwide1.5-2 million new cases of cutaneous leishmaniasis and 500,000 cases of visceral leishmaniasis are reported each year. Leishmaniasis is endemic in nearly 90 countries worldwide and close to 12 million new cases of leishmaniasis are reported worldwide annually. Studies on antileishmanial drug development is of major concern as leishmaniasis are the second largest parasitic killer in the world and the available drugs are either toxic or costly. The major surface GP63 protease, also known as Zinc- metalloproteases present on the surface of leishmanial promastigotes, can be targeted for drug development. Protease inhibitors targeting such surface proteases show promising results. Different protease inhibitors have been isolated from marine actinobacteria against many infectious diseases. Metabolites produced by these actinobacteria may have greater importance for the discovery and development of new antileishmanial drugs. Hence, this review discusses the background, current situation, treatment, and protease inhibitors from marine actinobacteria for drug development against GP63 molecules.

Larvicidal, repellent, and ovicidal activity of marine actinobacteria extracts against Culex tritaeniorhynchus and Culex gelidus.

The purpose of the present study was to assess the effect of crude extracts of marine actinobacteria on larvicidal, repellent, and ovicidal activities against Culex tritaeniorhynchus and Culex gelidus (Diptera: Culicidae). The early fourth instar larvae of C. tritaeniorhynchus and C. gelidus, reared in the laboratory, were used for larvicidal, ovicidal, and repellent assay with crude extracts of actinobacteria. Saccharomonospora spp. (LK-1), Streptomyces roseiscleroticus (LK-2), and Streptomyces gedanensis (LK-3) were identified as potential biocide producers. Based on the antimicrobial activity, three strains were chosen for larvicidal activity. The marine actinobacterial extracts showed moderate to high larvicidal effects after 24 h of exposure at 1,000 ppm and the highest larval mortality was found in extract of LK-3 (LC(50) = 108.08 ppm and LC(90) = 609.15 ppm) against the larvae of C. gelidus and (LC(50) = 146.24 ppm and LC(90) = 762.69 ppm) against the larvae of C. tritaeniorhynchus. Complete protections for 240 min were found in crude extract of LK-2 and LK-3 at 1,000 ppm, against mosquito bites of C. tritaeniorhynchus and C. gelidus, respectively. After 24-h treatment, mean percent hatchability of the ovicidal activity was observed. The percent hatchability was inversely proportional to the concentration of extract and directly proportional to the eggs. Crude extracts of LK-1 and LK-3 showed no hatchability at 1,000 ppm against C. tritaeniorhynchus and C. gelidus, respectively. This is an ideal ecofriendly approach for the control of Japanese encephalitis vectors, C. tritaeniorhynchus and C. gelidus.

Protease inhibitors as a potential agent against visceral Leishmaniasis: A review to inspire future study

Abstract Leishmaniasis is transmitted by sandfly which carries the intracellular protozoa in their midgut. Among visceral, cutaneous and mucocutaneous leishmaniasis, visceral type that is caused by Leishmania donovani is the most lethal one. Findings of leishmanial structure and species took place in 19th century and was initiated by Donovan. Leishmaniasis is still a major concern of health issues in many endemic countries in Asia, Africa, the Americas, and the Mediterranean region. Worldwide1.5-2 million new cases of cutaneous leishmaniasis and 500,000 cases of visceral leishmaniasis are reported each year. Leishmaniasis is endemic in nearly 90 countries worldwide and close to 12 million new cases of leishmaniasis are reported worldwide annually. Studies on antileishmanial drug development is of major concern as leishmaniasis are the second largest parasitic killer in the world and the available drugs are either toxic or costly. The major surface GP63 protease, also known as Zinc- metalloproteases present on the surface of leishmanial promastigotes, can be targeted for drug development. Protease inhibitors targeting such surface proteases show promising results. Different protease inhibitors have been isolated from marine actinobacteria against many infectious diseases. Metabolites produced by these actinobacteria may have greater importance for the discovery and development of new antileishmanial drugs. Hence, this review discusses the background, current situation, treatment, and protease inhibitors from marine actinobacteria for drug development against GP63 molecules.

Efficacy of Alpha Glucosidase Inhibitor from Marine Actinobacterium in the Control of Postprandial Hyperglycaemia in Streptozotocin (STZ) Induced Diabetic Male Albino Wister Rats.

The current study was carried out to evaluate the in-vitro and in-vivo efficiency of alpha glucosidase inhibitor of marine actinobacteria in the control of postprandial hyperglycaemia. Soil samples were collected from salterns, coastal area in Kothapatnam, Ongole, Andhra Pradesh, India. Among the actinobacterial isolates tested for yeastα-glucosidase inhibitory activity, only three isolates showed prominent inhibition. The patient isolate was selected and identified as Streptomyces coelicoflavus SRBVIT13 using 16S r-RNA gene sequencing. In in-vitro studies, the chloroform extract of Streptomyces coelicoflavus SRBVIT13 showed significant enzyme inhibitory activity against yeast and mammalian α-glucosidaseenzymes. In animal studies, the oral ingestion of chloroform extract (600 mg/kg) of S. coelicoflavus SRBVIT13 in maltose and sucrose loaded diabetic rats, showed significant regulation of postprandial blood glucose by 82.25% and a 77.25% reduction, respectively. The lead compound from S. coelicoflavusSRBVIT13 was isolated, purified, characterized, and identified by stranded analytical techniques as 2-t-butyl-5-chloromethyl-3-methyl-4-oxoimidazolidine-1-carboxylic acid, t-butyl ester. The results obtained in the present study are promising and the bioactive compound from S. coelicoflavusSRBVIT13 may be considered as a potential agent in regulating the postprandial hyperglycaemia.

Novel microbial route to synthesize ZnO nanoparticles using Aeromonas hydrophila and their activity against pathogenic bacteria and fungi.

In the present work, we describe a low-cost, unreported and simple procedure for biosynthesis of zinc oxide nanoparticles (ZnO NPs) using reproducible bacteria, Aeromonas hydrophila as eco-friendly reducing and capping agent. UV-vis spectroscopy, XRD, FTIR, AFM, NC-AFM and FESEM with EDX analyses were performed to ascertain the formation and characterization of ZnO NPs. The synthesized ZnO NPs were characterized by a peak at 374 nm in the UV-vis spectrum. XRD confirmed the crystalline nature of the nanoparticles and AFM showed the morphology of the nanoparticle to be spherical, oval with an average size of 57.72 nm. Synthesized ZnO NPs showed the XRD peaks at 31.75°, 34.37°, 47.60°, 56.52°, 66.02° and 75.16° were identified as (100), (002), (101), (102), (110), (112) and (202) reflections, respectively. Rietveld analysis to the X-ray data indicated that ZnO NPs have hexagonal unit cell at crystalline level. The size and topological structure of the ZnO NPs was measured by NC-AFM. The morphological characterization of synthesized nanoparticles was analyzed by FESEM and chemical composition by EDX. The antibacterial and antifungal activity was ended with corresponding well diffusion and minimum inhibitory concentration. The maximum zone of inhibition was observed in the ZnO NPs (25 µg/mL) against Pseudomonas aeruginosa (22±1.8 mm) and Aspergillus flavus (19±1.0 mm). Bacteria-mediated ZnO NPs were synthesized and proved to be a good novel antimicrobial material for the first time in this study.