The hidden treasures in endophytic fungi: a comprehensive review on the diversity of fungal bioactive metabolites, usual analytical methodologies, and applications.

This review provides a comprehensive overview of the key aspects of the natural metabolite production by endophytic fungi, which has attracted significant attention due to its diverse biological activities and wide range of applications. Synthesized by various fungal species, these metabolites encompass compounds with therapeutic, agricultural, and commercial significance. We delved into strategies and advancements aimed at optimizing fungal metabolite production. Fungal cultivation, especially by Aspergillus, Penicillium, and Fusarium, plays a pivotal role in metabolite biosynthesis, and researchers have explored both submerged and solid-state cultivation processes to harness the full potential of fungal species. Nutrient optimization, pH, and temperature control are critical factors in ensuring high yields of the targeted bioactive metabolites especially for scaling up processes. Analytical methods that includes High-Performance Liquid Chromatography (HPLC), Liquid Chromatography-Mass Spectrometry (LC-MS), Gas Chromatography-Mass Spectrometry (GC-MS), Nuclear Magnetic Resonance (NMR), and Mass Spectrometry (MS), are indispensable for the identification and quantification of the compounds. Moreover, genetic engineering and metabolic pathway manipulation have emerged as powerful tools to enhance metabolite production and develop novel fungal strains with increased yields. Regulation and control mechanisms at the genetic, epigenetic, and metabolic levels are explored to fine-tune the biosynthesis of fungal metabolites. Ongoing research aims to overcome the complexity of the steps involved to ensure the efficient production and utilization of fungal metabolites.

Use of geographical information systems (GIS) in assessing ecological profile, fish community structure and production of a large reservoir of Himachal Pradesh.

The present study demonstrates the spatial analysis and mapping of fish and different measures of environmental parameters and fish diversity of Pong reservoir, Himachal Pradesh, using Kriging spatial interpolation methods for geographical information system mapping. Seasonal data on environmental parameters, potential fish habitat and fish diversity was collected from lentic (dam), lentic (reservoir), transitional and lotic zone of the reservoir.. Important environmental parameters like water temperature, dissolved oxygen, electrical conductivity, water depth and transparency showed variations across the different zones of the reservoir. The sediment of the reservoir was sandy clay loam in nature as per texture analysis. Fish species richness, Shannon index and evenness index showed a similarity of the lotic and lentic (reservoir) zones of the reservoir. Six potential fish breeding grounds were identified in the reservoir indicating high conservation significance. The analysis of data showed a declining trend in fish production from 456.9 tonnes during the decade 1976-1987 to 347.91 tonnes during 2009-2020. The factors like anthropogenic climate change, predation of a stocked fish juvenile by water birds, undersized fish stocking and unscientific management are the probable reasons for the decreasing fish production. The spatial variation pattern of the water spread area, environmental parameters, fish catch and potential fish breeding grounds depicted in the GIS platform can be used as an important information base by the policy makers for fisheries management. The stocking of large size fish as a stocking material and adequate protection of the potential fish breeding grounds are the key advisories for the sustainable enhancement of fisheries as well as conservation.

An overview of rapamycin: from discovery to future perspectives.

Rapamycin is an immunosuppressive metabolite produced from several actinomycete species. Besides its immunosuppressive activity, rapamycin and its analogs have additional therapeutic potentials, including antifungal, antitumor, neuroprotective/neuroregenerative, and lifespan extension activities. The core structure of rapamycin is derived from (4R,5R)-4,5-dihydrocyclohex-1-ene-carboxylic acid that is extended by polyketide synthase. The resulting linear polyketide chain is cyclized by incorporating pipecolate and further decorated by post-PKS modification enzymes. Herein, we review the discovery and biological activities of rapamycin as well as its mechanism of action, mechanistic target, biosynthesis, and regulation. In addition, we introduce the many efforts directed at enhancing the production of rapamycin and generating diverse analogs and also explore future perspectives in rapamycin research. This review will also emphasize the remarkable pilot studies on the biosynthesis and production improvement of rapamycin by Dr. Demain, one of the world's distinguished scientists in industrial microbiology and biotechnology.

Analyzing and engineering of the biosynthetic pathway of mollemycin A for enhancing its production.

Mollemycin A (MOMA) is a unique glyco-hexadepsipeptide-polyketide that was isolated from a Streptomyces sp. derived from the Australian marine environment. MOMA exhibits remarkable inhibitory activity against both drug-sensitive and multidrug-resistant malaria parasites. Optimizing MOMA through structural modifications or product enhancements is necessary for the development of effective analogues. However, modifying MOMA using chemical approaches is challenging, and the production titer of MOMA in the wild-type strain is low. This study identified and characterized the biosynthetic gene cluster of MOMA for the first time, proposed its complex biosynthetic pathway, and achieved an effective two-pronged enhancement of MOMA production. The fermentation medium was optimized to increase the yield of MOMA from 0.9 mg L-1 to 1.3 mg L-1, a 44% boost. Additionally, a synergistic mutant strain was developed by deleting the momB3 gene and overexpressing momB2, resulting in a 2.6-fold increase from 1.3 mg L-1 to 3.4 mg L-1. These findings pave the way for investigating the biosynthetic mechanism of MOMA, creating opportunities to produce a wide range of MOMA analogues, and developing an efficient strain for the sustainable and economical production of MOMA and its analogues.

Multiphase Flow Production Enhancement Using Drag Reducing Polymers.

This paper presents a comprehensive experimental investigation concerning the effect of drag reducing polymers (DRP) on enhancing the throughput and reducing the pressure drop for a horizontal pipe carrying two-phase flow of air and water mixture. Moreover, the ability of these polymer entanglements to damp turbulence waves and changing the flow regime has been tested at various conditions, and a clear observation showed that the maximum drag reduction always occurs when the highly fluctuated waves were reduced effectively by DRP (and that, accordingly, phase transition (flow regime changed) appeared. This may also help in improving the separation process and enhancing the separator performance. The present experimental set-up has been constructed using a test section of 1.016-cm ID; an acrylic tube section was used to enable visual observations of the flow patterns. A new injection technique has been utilized and, with the use of different injection rates of DRP, the results have shown that the reduction in pressure drop occurred in all flow configurations. Furthermore, different empirical correlations have been developed which improve the ability to predict the pressure drop after the addition of DRP. The correlations showed low discrepancy for a wide range of water and air flow rates.

Roles of zero-valent iron in anaerobic digestion: Mechanisms, advances and perspectives.

With the rapid growth of population and urbanization, more and more bio-wastes have been produced. Considering organics contained in bio-wastes, to recover resource from bio-wastes is of great significance, which can not only achieve the resource recycle, but also protect the environment. Anaerobic digestion (AD) has been proved as one of the most promising strategies to recover bio-energy from bio-wastes, as well as to realize the reduction of bio-wastes. However, the conventional interspecies electron transfer is sensitive to environmental shocks, such as high ammonia, organic pollutants, metal ions, etc., which lead to instability or failure of AD. The recent findings have proved that the introduction of zero-valent iron (ZVI) in AD system can significantly enhance methane production from bio-wastes. This review systematically highlighted the recent advances on the roles of ZVI in AD, including underlying mechanisms of ZVI on AD, performance enhancement of AD contributed by ZVI, and impact factors of AD regulated by ZVI. Furthermore, current limitations and outlooks have been analyzed and concluded. The roles of ZVI on underlying mechanisms in AD include regulating reaction conditions, electron transfer mode and function of microbial communities. The addition of ZVI in AD can not only enhance bio-energy recovery and toxic contaminants removal from bio-wastes, but also have the potential to buffer adverse effect caused by inhibitors. Moreover, the electron transfer modes induced by ZVI include both interspecies hydrogen transfer and direct interspecies electron transfer pathways. How to comprehensively evaluate the effects of ZVI on AD and further improve the roles of ZVI in AD is urgently needed for practical application of ZVI in AD. This review aims to provide some references for the introduction of ZVI in AD for enhancing bio-energy recovery from bio-wastes.

Cytidine-containing tails robustly enhance and prolong protein production of synthetic mRNA in cell and in vivo.

Synthetic mRNAs are rising rapidly as alternative therapeutic agents for delivery of proteins. However, the practical use of synthetic mRNAs has been restricted by their low cellular stability as well as poor protein production efficiency. The key roles of poly(A) tail on mRNA biology inspire us to explore the optimization of tail sequence to overcome the aforementioned limitations. Here, the systematic substitution of non-A nucleotides in the tails revealed that cytidine-containing tails can substantially enhance the protein production rate and duration of synthetic mRNAs both in vitro and in vivo. Such C-containing tails shield synthetic mRNAs from deadenylase CCR4-NOT transcription complex, as the catalytic CNOT proteins, especially CNOT6L and CNOT7, have lower efficiency in trimming of cytidine. Consistently, these enhancement effects of C-containing tails were observed on all synthetic mRNAs tested and were independent of transfection reagents and cell types. As the C-containing tails can be used along with other mRNA enhancement technologies to synergically boost protein production, we believe that these tails can be broadly used on synthetic mRNAs to directly promote their clinical applications.

Production enhancement and characterization of the polyhydroxyalkanoate produced by Natrinema ajinwuensis (as synonym) ≡ Natrinema altunense strain RM-G10.

Application of halophiles can decrease the cost of polyhydroxyalkanoate (PHA) production or bioplastic which are an alternative to the petroleum-derived plastic. Extremely halophilic archaeon, Natrinema ajinwuensis RM-G10 accumulated 61.02±0.68% PHA of its cell dry mass at 72h in repeated batch cultures yielding 0.210±0.001gL-1h-1 volumetric productivity after selection of the best cultivation conditions. Transmission electron microscopy showed the presence of PHA granules inside the archaeal cells. Characterization by gas chromatographic analysis, gas chromatographic- mass spectrophotometric analysis, thermogravimetric analysis, differential scanning calorimetric analysis, X-ray diffraction analysis, Fourier transform infra red spectroscopy and nuclear magnetic resonance spectroscopy revealed the polymer to be poly(3-hydroxybutyrate-co-3-hydroxyvalerate) with 13.93mol% 3-hydroxyvalerate content and having 35.45% crystallinity, -12.3°C glass transition temperature, 143°C and 157.5°C melting temperatures and 284°C degradation temperature. This is the first report on production enhancement (on a small scale) and characterization of the polyhydroxyalkanoate produced by Natrinema ajinwuensis (as synonym) ≡ Natrinema altunense strain RM-G10 and the Natrinema genus in general.

Biogas production enhancement using semi-aerobic pre-aeration in a hybrid bioreactor landfill.

Landfilling continues to be one of the main methods used in managing Municipal Solid Waste (MSW) worldwide, particularly in developing countries. Although in many countries national legislation aims to reduce this practice as much as possible, landfill is a necessary and unavoidable step in closing the material cycle. The need for innovative waste management techniques to improve landfill management and minimize the adverse environmental impact produced has resulted in an increasing interest in innovative systems capable of accelerating waste stabilization. Landfill bioreactors allow decomposition kinetics to be increased and post-operational phase to be shortened; in particular, hybrid bioreactors combine the benefits afforded by both aerobic and anaerobic processes. Six bioreactor simulators were used in the present study: four managed as hybrid, with an initial semi-aerobic phase and a second anaerobic phase, and two as anaerobic control bioreactors. The main goal of the first aerated phase is to reduce Volatile Fatty Acids (VFA) in order to increase pH and enhance methane production during the anaerobic phase; for this reason, air injection was stopped only when these parameters reached the optimum range for methanogenic bacteria. Biogas and leachate were constantly monitored throughout the entire methanogenic phase with the aim of calibrating a Gompertz Model and evaluating the effects of pre-aeration on subsequent methane production. The results showed that moderate and intermittent pre-aeration produces a positive effect both on methane potential and in the kinetics of reaction.

Strategies for enhancing fermentative production of acetoin: a review.

Acetoin is a volatile compound widely used in foods, cigarettes, cosmetics, detergents, chemical synthesis, plant growth promoters and biological pest controls. It works largely as flavour and fragrance. Since some bacteria were found to be capable of vigorous acetoin biosynthesis from versatile renewable biomass, acetoin, like its reduced form 2,3-butanediol, was also classified as a promising bio-based platform chemical. In spite of several reviews on the biological production of 2,3-butanediol, little has concentrated on acetoin. The two analogous compounds are present in the same acetoin (or 2,3-butanediol) pathway, but their production processes including optimal strains, substrates, derivatives, process controls and product recovery methods are quite different. In this review, the usages of acetoin are reviewed firstly to demonstrate its importance. The biosynthesis pathway and molecular regulation mechanisms are then outlined to depict the principal network of functioning in typical species. A phylogenetic tree is constructed and the relationship between taxonomy and acetoin producing ability is revealed for the first time, which will serve as a useful guide for the screening of competitive acetoin producers. Genetic engineering, medium optimization, and process control are effective strategies to improve productivity as well. Currently, downstream processing is one of the main barriers in efficient and economical industrial acetoin fermentation. The future prospects of microbial acetoin production are discussed in light of the current progress, challenges, and trends in this field.