Pharmaceutical Use Research Articles

Unveiling the Drug Formulation Code: A Journey to Three-Dimensional Precision.

Magistral formulations emerged years ago and were of great help in the personalization of treatments for patients. Over time, innovation began in this area with new technologies such as three-dimensional (3D) printing, which has brought greater benefits, ease of preparation, new scopes, and even cost reduction. Three-dimensional printing of medicines opened the way to create personalized multi-dose, controlled-release, multi-drug tablets, among others. In addition, this technology manages to be more specific in adjusting pharmacokinetics, doses, and even organoleptic qualities, which is precisely what is sought since the medication is being personalized for a patient due to a particular case or condition. Throughout the research, some studies can be observed that function as a base that provides safety and effectiveness for the subsequent use of other pharmaceuticals in the 3D printing of medicines.

Ortaçağ Anadolu Türk Uygarlığında At Kökenli Ürünlerin Terapötik Kullanımı

Bu çalışmada, Ortaçağ Anadolu Türk uygarlığında atın çeşitli uzuvlarının yanı sıra atlardan elde edilen et, süt, mâye gibi gıdaların sağlık alanında kullanılmasını, ayrıca döneme özgü hipoterapi uygulamaları araştırılmıştır. Çalışmamızda on üçüncü ve on beşinci yüzyıllar arasında Anadolu’da Türkçe kullanılarak yazılan, derlenen ve tercüme edilen eserler kullanılmıştır. Bulgularımıza göre, binicilik bir tedavi yöntemi olarak tavsiye edilmiş, ayrıca atın kılı, toynağı, derisi, gübresi, kemiği, dişi, kılı, kanı, iliği, içyağı, eti ve sütü sağlık alanında kullanılmıştır. İslâm dinine göre dâhili kullanımları yasak ya da şüpheli olan şarap ile at kanı ve at eti gibi maddelerin, insan sağlığı öncelenerek önerildiği görülmüştür. Ortaçağ Anadolu Türk uygarlığı kaynaklarında at kökenli ürünlerin tedavi amaçlı kullanımının Antik Yunan ve Ortaçağ İslâm eserlerindeki kullanımları ile uyumlu olduğu, öte yandan özgün kullanım sahaları da geliştirdiği tespit edilmiştir. Kaynaklarda, Plinius’un kaydettiği at kökenli ürünlerin kullanım örneklerinin bir bölümünün yer almadığı da saptanmıştır. Bu, Ortaçağ’da Klasik Antikite uygarlığı eserlerinin Arapçaya tercüme edilirken Yunanca eserlere ağırlık verilmiş olmasının sonucudur. Ortaçağ Anadolu Türk uygarlığı yazınında gelişmiş bir at kültürünün bulunduğu, atın morfolojisi ile sembolojisine dair zengin bir tanım çeşitliliğin yanı sıra, at besleyiciliği, yetiştiriciliği ve biniciliğinin övüldüğü, ayrıca at kökenli ürünlerin sağlık alanında kullanıldığı görülmüştür.

Ulvans, sulfated β-d-galactans and xyloarabinogalactan: A comparative approach to extraction, structural characterization and antioxidant activity assessment

Antioxidants can be extracted from various seaweeds as natural ingredients for use in foods, cosmetics, and pharmaceuticals. The composition and structure of polysaccharides extracted from four green seaweeds: Ulva lactuca (UL), Halimeda opuntia (HO), Caulerpa racemosa (CR) and Chaetomorpha antennina (CA) were correlated with their antioxidant activities. Crude extracts were characterized by NMR (1H and 13C), HP-SEC, HPAEC-PAD and FTIR spectroscopy. Extracted polysaccharides were assayed spectrophotometrically for their total sugar, sulfate, phenolic and protein contents. The antioxidant capacities of each fractionated polysaccharide sample were evaluated by five methods, i.e., ABTS (2,2-azino-bis-[3-ethylbenzothiazoline-6-sulfonic acid]), DPPH (2,2-diphenyl-1-picrylhydrazyl radical), ferric-reducing power in FRAP (Ferric-reducing Antioxidant Power), superoxide dismutase (SOD), and the hydroxyl radical (OH) scavenging capacity assay. All polysaccharides had molecular weights (MW) under 1000 kDa, with HO having the lowest MW (<100 kDa). Polysaccharide extracts of UL (i.e., l-iduronic acid, 1,4-linked α-l-rhamnose, β-d-glucuronic acid) and CA were promising sources of antioxidants. The highest antioxidant capacity was measured in extracts from CA-2B (52.1 ± 0.9 μg/mL) using the ABTS assay, while CR-1B exhibited the highest antioxidant activity in both the FRAP (303.7 ± 8.2 μm/mL) and OH (28.4 ± 0.8%) assays. Taken together, useful insights were gained into the potential health benefits of selected green seaweed polysaccharides (i.e., ulvans, sulfated or/and pyruvylated β-d-galactans and sulfated xyloarabinogalactan) for applications in the pharmaceutical, food and biotechnology industries.

Urban Wastewater-Based Surveillance of SARS-CoV-2 Virus: A Two-Year Study Conducted in City of Patras, Greece.

Wastewater-based epidemiology, during the COVID-19 pandemic years, has been applied as a complementary approach, worldwide, for tracking SARS-CoV-2 virus into the community and used as an early warning of the prevalence of COVID-19 infection. The present study presents the results of the 2-year surveillance project, in the city of Patras, Greece. The purpose of the study was to monitor SARS-CoV-2 and implement WBE as an early warning method of monitoring Public Health impact. The presence of SARS-CoV-2 was determined and quantified in 310 samples using RT-qPCR assays. For the years 2022 and 2023, 93.5% and 78.7% of samples were found positive, respectively. Comparison of detection methods have been conducted to select the method with the highest recovery of the viral load. A seasonal variation of the virus was recorded, showing a recession in summer months confirming the country's epidemiological data as indicated by positive correlation of wastewater viral load with registered cases of COVID-19 infections during these years (p < 0.05) and moreover sealed with a significant negative correlation observed with Daily Average (p < 0.01) and Daily Maximum Temperature (p < 0.01). More research was carried out to elucidate a possible association of physicochemical characteristics of wastewater with viral load showing positive correlation with Chlorides (p < 0.01) advocating possible increased use of chlorine-based disinfectants and Electrical Conductivity (p < 0.01) indicates that wastewater during periods of increased infections is more heavily loaded with ions from chemical and biological pollutants. No correlation found with rainfall and physicochemical indicators, such as COD, BOD5, Total Phosphorus, Total Nitrogen, and Total Suspended Solids. According to the findings, WBE represents a useful tool in the management of epidemics based on an environmental approach and it can also shed light on the interacting parameters that capture Public Health since any infections that may lead to epidemics lead to a parallel change in the use of pharmaceuticals, antimicrobials, disinfectants, and microbial load in urban wastewater.

Optimizing skin wound healing: The crucial role of the innate immune system and inflammatory microenvironment

Skin, as a part of the innate immune system, represents the first line of defense against pathogens. Each mechanical damage to the skin surface disrupts its homeostasis, thus rapidly inducing the cascade of repair processes. Wound healing comprises 4 subsequent and overlapping steps: hemostasis, inflammation, proliferation, and remodeling. The interplay of the abovementioned phases results in successful cell restoration and tissue repair. The efficiency of wound healing depends on numerous internal and external factors. The proper recruitment of immune cells, such as neutrophils and macrophages, and their interactions with keratinocytes, fibroblasts, and extracellular matrix (ECM) accounts for one of the most significant elements affecting this process. Despite the interaction of the immune cells, the development of a highly favorable microenvironment surrounding the damaged area also constitutes a vital component of successful healing. These optimal conditions combined with the inflow of stimuli, such as cytokines and growth factors, lead to complete wound closure and skin surface restoration. Nevertheless, in order to increase the efficiency of wound healing treatment and improve existing technologies, it is essential to gain a deeper understanding of the healing steps’ complexity. In this work, we elucidated basic mechanisms regarding skin injury sealing with a focus on the creation of a highly beneficial inflammatory microenvironment. The presented paper outlines current approaches to managing the excessive inflammation of the skin wound microenvironment to improve the treatment of chronic wounds. The most important perspectives in immunology phase modulation include the use of pharmaceuticals, natural bioactive compounds, immunomodulatory scaffolds, skin substitutes, cell-based therapies, and growth factors or cytokines injections.

A survey of C–C bond formation strategies and mechanism deployed by iron-containing enzymes in natural products

Developing effective carbon-carbon bond forming strategies is one of the central topics for organic chemistry, boosting the development of synthetic methods towards complex molecule preparation. Meanwhile, enzymes, biocatalysts existing in nature, can facilitate a stunning array of cyclization reactions through C–C bond formation, in which these late stage ‘‘decorations’’ are essential for inherent bioactivity and pharmaceutical use. In this review, we discuss how iron-containing enzymes catalyze intramolecular C–C bond formations found in natural products. Several of these enzymatic processes serve as foundations in developing chemo-enzymatic strategies in complex molecule synthesis.

STUDY OF THE SAFETY OF GRAIN POST-ALCOHOLIC GRAIN

Introduction. When producing alcohol, only the starch is extracted from the grain; the remainder of the grain containing various biologically active substances (BAS): proteins and amino acids, reducing substances, uronides, flavonoids, lipids, vitamins and provitamins, with added enzymes is called post-alcohol grain grains, its volume is 12-13 times greater than the volume of alcohol and practically not used. To substantiate the prospects for the pharmaceutical use of grains, two areas of processing have been proposed: to obtain total biologically active substances (“Biobardins”) and in-dividual betaine hydrochlorides with different pharmacological properties. The assumption that the cause of grains spoilage is labile biologically active substances, the isolation of which will determine the stability of grains, requires experimental confirmation. The purpose of the work is to study the chemical and microbiological safety of grains (wheat, corn, barley, millet) before and after its processing (after obtaining Biobardins and betaines). Material and methods. The object of the study is various types of grain grounds (wheat, corn, barley, millet) produced in 2021–2022 by distilleries in the Stavropol Territory. We studied the chemical safety of industrial waste according to the integral and most informative indicator of anthropogenic environmental pollution - the indicator “chemical oxygen consumption” (COC), determined by dichromatometry. Microbiological quality control of grain grounds was carried out in accordance with the requirements of general pharmacopoeial monograph GPM.1.2.4.0002.18 “Microbiological purity” of the State Pharmacopoeia of the Russian Federation XIV. Results. The indicator of “chemical oxygen consumption” (COC), which characterizes the chemical safety of waste and determined by dichromatome-try, decreased by 4.1 times (by 75.6%) when obtaining Biobardinov from stillage (from 54503 to 13205 mg O/l), and when obtaining betaines - 3.5 times (by 71.4%) (from 54503 to 15490 mg O/l). In both options, the recycled grains corresponds to non-hazardous industrial waste. According to the results of specific qualitative reactions, the processed grains contains no biologically active substances characteristic of the original grains: proteins and amino acids, reducing sugars, uronides. Microbiological control of the processed grains also confirmed its microbiological safety in terms of the content of aerobic bacteria, enterobacteria, fungi and the absence of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella. Conclusion. Thus, the use of various types of post-alcohol grain grains as pharmaceutical raw materials for the production of total and individual medicines made it possible to solve 2 problems: to use grains as a medicinal raw material and to reduce the technogenic impact of grains on the en-vironment.

Chronobiology of Viscum album L.: a time series of daily metabolomic fingerprints spanning 27years.

Introduction: European mistletoe (Viscum album L.) has been gaining increasing interest in the field of oncology as a clinically relevant adjunctive treatment in many forms of cancer. In the field of phytopharmacology, harvesting time is pivotal. In the last century, a form of metabolomic fingerprinting based on pattern formation was proposed as a way to determine optimal harvesting times to ensure high quality of mistletoe as raw material for pharmaceutical use. In order to further evaluate the information obtained with this metabolomic fingerprinting method, we analysed a large time series of previously undigitised daily mistletoe chromatograms dating back to the 1950s. Methods: These chromatograms were scanned and evaluated using computerized image analysis, resulting in 12 descriptors for each individual chromatogram. We performed a statistical analysis of the data obtained, investigating statistical distributions, cross-correlations and time self-correlations. Results: The analysed dataset spanning about 27years, contains 19,037 evaluable chromatograms in daily resolution. Based on the distribution and cross-correlation analyses, the 12 descriptors could be clustered into six independent groups describing different aspects of the chromatograms. One descriptor was found to mirror the annual rhythm being well correlated with temperature and a phase shift of 10days. The time self-correlation analysis showed that most other descriptors had a characteristic self-correlation of ∼50days, which points to further infradian rhythms (i.e., more than 24h). Discussion: To our knowledge, this dataset is the largest of its type. The combination of this form of metabolomic fingerprinting with the proposed computer analysis seems to be a promising tool to characterise biological variations of mistletoe. Additional research is underway to further analyse the different rhythms present in this dataset.

Establishment of human induced pluripotent stem cell-derived hepatobiliary organoid with bile duct for pharmaceutical research use

In vitro models of the human liver are promising alternatives to animal tests for drug development. Currently, primary human hepatocytes (PHHs) are preferred for pharmacokinetic and cytotoxicity tests. However, they are unable to recapitulate the flow of bile in hepatobiliary clearance owing to the lack of bile ducts, leading to the limitation of bile analysis. To address the issue, a liver organoid culture system that has a functional bile duct network is desired. In this study, we aimed to generate human iPSC-derived hepatobiliary organoids (hHBOs) consisting of hepatocytes and bile ducts. The two-step differentiation process under 2D and semi-3D culture conditions promoted the maturation of hHBOs on culture plates, in which hepatocyte clusters were covered with monolayered biliary tubes. We demonstrated that the hHBOs reproduced the flow of bile containing a fluorescent bile acid analog or medicinal drugs from hepatocytes into bile ducts via bile canaliculi. Furthermore, the hHBOs exhibited pathophysiological responses to troglitazone, such as cholestasis and cytotoxicity. Because the hHBOs can recapitulate the function of bile ducts in hepatobiliary clearance, they are suitable as a liver disease model and would be a novel in vitro platform system for pharmaceutical research use.

The Implementation and Optimization of Neonatal Epidural Analgesia in a Tertiary Care Hospital: A Technical Report.

Effective analgesic therapy in neonates continues to be fundamental for improving quality of life and decreasing the need for further medical intervention. When pain is not well controlled in the neonatal intensive care setting, we see an increased use of sedation pharmaceuticals, mechanical ventilation, and altered somatosensory development, among other complications. Currently, there is no standardized protocol addressing effective pain management while decreasing the need for further sedation. In this article, we seek to demonstrate how our institution standardized and implemented the utilization of epidural analgesia in neonates as the preferred method of pain management for open thoracic and abdominal surgeries.

Chemical and Bioactive Properties of Red Rice with Potential Pharmaceutical Use.

Red rice has been proposed as a super-food. Accordingly, the nutritional properties (AOAC), as well as its chemical composition, including sugars (HPLC-RI), organic acids (UFLC-PDA), tocopherols (HPLD-FD), and phenolic compounds (LC-DAD-ESI/MSn), together with the main bioactive properties (antioxidant, cytotoxic, antiproliferative, and antibacterial activities), were evaluated to access its nutritional benefits and health improvement potential. The most abundant macronutrients found were carbohydrates (87.2 g/100 g dw), proceeded by proteins (9.1 g/100 g dw), fat (2.6 g/100 g dw), and ash (1.1 g/100 g dw). Sucrose and raffinose were the only detected sugars, with sucrose presenting the maximum concentration (0.74 g/100 g dw). MUFAs and PUFAs were the predominant fatty acids (40.7% and 31%, respectively). Among the two detected tocopherol isoforms, γ-tocopherol (0.67 mg/100 g dw) predominated over α-tocopherol. The phenolic compounds profile, majorly composed of flavan-3-ols, should be associated with the detected bioactivities, which may provide biological benefits to human health beyond the primary nutritional effect. Overall, the bioactive potential of red rice was comprehensively accessed.

Sources of Cysteine-Based Pharmaceutical Drugs and Their Halal Aspects in Pharmaceutical Product Development

Indonesia is the country with the largest Muslim population in the world, so supplements and medicines consumed must be halal (permissible in Islamic law). Cysteine is an essential amino acid that is crucial to human biological functions. Cysteine can be used as a mucolytic agent to help thin mucus in respiratory diseases such as bronchitis or chronic obstructive pulmonary disease (COPD). It also serves as an antidote to acetaminophen for detoxification purposes or as an antidote to counteract paracetamol (acetaminophen) overdose, a commonly used drug to relieve pain and reduce fever. Additionally, it functions as a supplement. This research aims to comprehensively review the sources of cysteine, its production, and its use in pharmaceuticals, as well as the opinions of scholars regarding the halal aspects that need to be considered in developing pharmaceutical products containing cysteine. The methods employed include searching through references from research articles obtained from Google Scholar, ScienceDirect, NCBI, Elsevier, and the Qur'an, Hadiths, and other Islamic literature sources. The compound structures are depicted using the ChemSketch tool from ACD/Labs. Mucolytic and acetaminophen drugs, such as acetylcysteine, can be derived from both animal and plant sources through chemical and non-chemical separation processes. Cysteine is generally a precursor for the synthesis of acetylcysteine. Cysteine sourced from specific organs, such as pig hair, has differing opinions among various scholars regarding its permissibility. However, the prevailing view and fatwa tend to lean towards its prohibition, depending on the source, process, and urgency of its use.

Cistus, Acacia, and Lemon verbena Valorization through Response Surface Methodology: Optimization Studies and Potential Application in the Pharmaceutical and Nutraceutical Industries.

Cistus ladanifer L., Acacia dealbata L., and Aloysia citrodora Paláu were subject to an optimization procedure for two extraction techniques (heat-assisted extraction (HAE) and ultrasound-assisted extraction (UAE)). The extracts were then analyzed by HPLC-DAD-ESI/MS for their phenolic profile (cistus-15 compounds, acacia-21 compounds, and lemon verbena-9 compounds). The response surface methodology was applied, considering four varying factors: ethanol percentage; extraction time; temperature/power; and S/L ratio, generating two responses (the major phenolic compound, or family of compounds, and the extraction yield). For cistus, both techniques optimized the extraction yield of punicalagins, with UAE proving to be the most efficient extraction method (3.22% ethanol, 22 min, 171 W, and 35 g/L). For acacia, HAE maximized the extraction of procyanidin (74% ethanol, 86 min, 24 °C, and 50 g/L), and UAE maximized the content of myricetin (65% ethanol, 8 min, 50 W, and 50 g/L). For lemon verbena, HAE favored the extraction of martynoside (13% ethanol, 96 min, 49 °C and 17 g/L) and forsythiaside UAE (94% ethanol, 25 min, 399 W, and 29 g/L). The optimal conditions for the extraction of compounds with high added value and potential for use in pharmaceuticals and nutraceuticals were defined.

Molecular Docking and ADMET Study of Phytochemicals as Anticancer Agent towards Alpha 1- Antichymotrypsin Variant DBS-II and Oxidised Quinone Reductase-2

Molecular Docking and ADMET Study of Phytochemicals as Anticancer Agent towards Alpha 1- Antichymotrypsin Variant DBS-II and Oxidised Quinone Reductase-2

Status and trends of legislative and regulatory regulation of off-label use of drugs: A review

The off-label use of drugs is a common practice worldwide. The legal basis for off-label medical use varies from country to country. Regulatory control of the pharmaceutical market in the off-label preventive and therapeutic practice at the international and national levels has become a breakthrough with the emergence of the coronavirus pandemic. The prospects for off-label use in the context of innovations in the legislation of public health in the Russian Federation are crucial. Professionally significant aspects of the use of medicinal products outside the Summary of Product Characteristics and the off-label use have been introduced by supranational regulatory authorities for the common market of medicinal products of the Eurasian Economic Union. Special attention should be paid to the regulatory control of the use of extemporaneous medicines as part of improving the government regulation of drug compounding in pharmacies. The active development of pharmacy activities in drug compounding within the framework of improving regulatory practice determines the relevance of actual off-label prescriptions and the use of extemporaneous formulations. Aim – to perform a systematic analysis of national, transnational legislative and regulatory documents regulating off-label use of medicinal products, determine the main conceptual components of the current regulatory pool and directions for future development in this area. Systematic analysis of the national legislative and regulatory pool of documents and the regulatory framework of the common market of medicinal products of the Eurasian Economic Union on the regulation of various aspects of the off-label use of medicinal products. Study of the components and identification of the main trends in the regulatory practice of prescriptions outside the Summary of Product Characteristics and the off-label use. An analytical search was carried out in the reference legal systems "ConsultantPlus" and "Garant" on the official websites of the Ministry of Health of Russia, the Eurasian Economic Union, the RusMed information resource of the National Library resource of Russia in medicine and pharmacy "Central Scientific Medical Library" was used. A logical generalization of the results on the current state of the legal framework and the development of conceptual proposals on the key directions of the prospective development of regulation, control, and supervisory activities of the pharmaceutical off-label use of medicinal products was made.

Trace compounds in the urban water cycle in the Freiberg region, Germany

Trace compounds in the urban water cycle in the Freiberg region, Germany

Effect of Lacticaseibacillus rhamnosus L08 fermentation on xanthine oxidase inhibitory activity and flavour profile of honeysuckle (Lonicera japonica thunb.)

Xanthine oxidase (XOD) catalyses the oxidation of hypoxanthine and xanthine to uric acid, and inhibition of its activity has become the main strategy to reduce uric acid production. Honeysuckle (HON) which is rich in polyphenols potentially has the capacity to inhibit XOD activity. However, it carries the bitter and astringent flavor as well as many traditional Chinese medicines, along with that most of the polyphenols in HON exist in bound form, the exploitation and application of HON in food is limited. In this study, we investigated the effects of Lacticaseibacillus rhamnosus L08 fermentation on the bioactive components, XOD inhibitory activity and flavour characteristics of HON. The results showed that the XOD inhibitory activity was increased by 2.08 times after 96 h of fermentation. It was demonstrated that the increase in the total flavonoid content and total phenol content was the main reason for the enhancement of the fermentation solution's XOD inhibitory activity and antioxidant activity. Moreover, the fermentation also enriched the composition of volatile components of HON and reduced levels of undesirable flavour substances, which made the usage of fermented HON as functional food or in pharmaceutical use feasible and applicable.

Antioxidant and Physical Characteristics of Anthocyanin Extract from Purple Yam (Dioscorea alata L.) Nanoencapsulation: Effect of Maltodextrin and Whey Protein Isolate Ratios

Anthocyanins are bioactive compounds with antioxidant, anti-inflammatory, and anti-diabetic activities. This bioactive compound is susceptible to changes in temperature and pH conditions. Its use in food products is also limited. Therefore, protection efforts that can bring anthocyanins into the food system through encapsulation are needed. Encapsulation is a technique for protecting bioactive compounds by coating the mixtures using biomaterials. The spray drying encapsulation process does not require difficult preparation and has good protection capabilities. The goal of this study was to investigate the encapsulating properties of the ratio of whey protein isolate to maltodextrin. This study used maltodextrin : whey protein isolate ratios (MD: WPI) 1:3, 1:1, and 3:1 (w/w). Anthocyanin extract was added 30% (w/w). The mixtures were powdered by drying them with a spray drier. The results showed that MD: WPI = 1:3 can retain more bioactive components than other treatments. The characteristics of nanoencapsulants in antioxidant activity, total phenol content, and anthocyanin were 65.16 + 2.87 %RSA, 776.25 + 45.23 mg GAE/100 g, 60.83 + 1.56 mg/100 g, respectively. The nanoencapsulations had irregular round morphology, particle size and zeta-potential were 301.3 nm and -31.9 mV, respectively. Therefore, anthocyanin encapsulation from purple yam extract was successfully produced with lower-cost material for food and pharmaceutical use.

Optimisation of polyphenol extraction for the valorisation of spent gin botanicals

An average of 0.21 kg spent gin botanicals (SGB) is generated for every 1 L of gin, making it the major by-product of gin distillation. The present circular economy dynamics and increased awareness on resource use presents an opportunity for valorisation of SGB. SGB was optimised for polyphenol extraction using a three-factor Box-Behnken Design in response surface methodology (RSM). This was used to both optimise and study how the extraction variables affected yields and values of polyphenol and antioxidant activity of SGB. The generated optimum conditions for polyphenol extraction from SGB were 50% (v/v) solvent concentration, 40 mL g−1 solvent: sample ratio, and 65 °C temperature. There is demand for polyphenols and natural antioxidants for use in both food and pharmaceuticals, and SGB is a natural bioresource material. The results from this study have shown a possible valorisation route for SGB and its potential for polyphenol extraction. This will create a sustainable pathway for the management of SGB and provide agro allied industries with a sustainable source of polyphenol. It will also provide a basis for process optimisation during gin distillation and possibility for reuse of botanicals materials.

Combinatorial biosynthesis for the engineering of novel fungal natural products.

Natural products are small molecules synthesized by fungi, bacteria and plants, which historically have had a profound effect on human health and quality of life. These natural products have evolved over millions of years resulting in specific biological functions that may be of interest for pharmaceutical, agricultural, or nutraceutical use. Often natural products need to be structurally modified to make them suitable for specific applications. Combinatorial biosynthesis is a method to alter the composition of enzymes needed to synthesize a specific natural product resulting in structurally diversified molecules. In this review we discuss different approaches for combinatorial biosynthesis of natural products via engineering fungal enzymes and biosynthetic pathways. We highlight the biosynthetic knowledge gained from these studies and provide examples of new-to-nature bioactive molecules, including molecules synthesized using combinations of fungal and non-fungal enzymes.