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Endophytic fungi represent a significant renewable resource for the discovery of pharmaceutically important compounds, offering substantial potential for new drug development. Their ability to address the growing issue of drug resistance has drawn attention from researchers seeking novel, nature-derived lead molecules that can be produced on a large scale to meet global demand. Recent advancements in genomics, metabolomics, bioinformatics, and improved cultivation techniques have significantly aided the identification and characterization of fungal endophytes and their metabolites. Current estimates suggest there are approximately 1.20 million fungal endophytes globally, yet only around 16% (190,000) have been identified and studied in detail. This underscores the vast untapped potential of fungal endophytes in pharmaceutical research. Research has increasingly focused on the transformation of bioactive compounds by fungal endophytes through chemical and enzymatic processes. A notable example is the anthraquinone derivative 6-O-methylalaternin, whose cytotoxic potential is enhanced by the addition of a hydroxyl group, sharing structural similarities with its parent compound macrosporin. These structure-bioactivity studies open up new avenues for developing safer and more effective therapeutic agents by synthesizing targeted derivatives. Despite the immense promise, challenges remain, particularly in the large-scale cultivation of fungal endophytes and in understanding the complexities of their biosynthetic pathways. Additionally, the genetic manipulation of endophytes for optimized metabolite production is still in its infancy. Future research should aim to overcome these limitations by focusing on more efficient cultivation methods and deeper exploration of fungal endophytes’ genetic and metabolic capabilities to fully harness their therapeutic potential. Graphical Abstract

Phytoplankton photoacclimation is a well‐documented response to changes in light and nutrient availability, with the Chlorophyll a to phytoplankton Carbon ratio (θ$\\theta $  = Chl: Cphyto${\\mathrm{C}}_{\\text{phyto}}$ ) increasing at low light and decreasing under high light to optimize growth rate. Accurate estimation of phytoplankton growth rates and Net Primary Production (NPP) from space requires knowledge of θ$\\theta $ , but cloud cover creates gaps. Current NPP models fill in the gaps by interpolating Chl (and other inputs) from clear‐sky pixels, ignoring the possibility of photoacclimation underneath clouds. Using data from ≈${\\approx} $ 9,000 matchups between BioGeoChemical‐Argo floats and cloud cover from the Moderate Resolution Imaging Spectroradiometer, we compared the response of θ$\\theta $to irradiances under cloudy and clear skies. We found that phytoplankton photoacclimate similarly regardless of sky conditions at the global scale. This study highlights an incorrect assumption in current NPP estimates and suggests ways to improve global assessments of both chlorophyll and NPP. Plain Language Summary Phytoplankton, like plants on land, change their pigment concentration in response to light and nutrient levels. Under high light, they have fewer photosynthetic pigments in their cells and more when under low light (assuming nutrients are plentiful), a process referred to as photoacclimation. Phytoplankton productivity is commonly computed as a function of pigment concentration and incoming solar radiation, hence the importance of accurately characterizing photoacclimation when evaluating oceanic productivity. At any given time ≈${\\approx} $ 70% of the ocean is cloudy, with productivity algorithms applied equally under both cloudy and clear skies. Due to the inability of satellites to collect surface data under clouds, productivity algorithms must estimate data under clouds based on clear sky pixels. Currently, they do so by interpolating the concentration of pigments in clear sky pixels. Thus, when clouds reduce radiations reaching the ocean (which they do at spatially large scales), the resulting cloudy productivity is reduced. Here we show, using data from satellites and automated observations from profiling floats, that phytoplankton cells adjust their pigmentation to the reduced light under cloud cover, thereby reducing the impact of clouds on productivity. This work provides a simple pathway to remove a bias in oceanic productivity estimates. Key Points At the global scale, phytoplankton exhibit similar photoacclimation responses under both cloudy and clear skies Seasonal variations in photoacclimation occur, but these changes are mostly consistent between sky conditions Neglecting photoacclimation under clouds likely leads to a significant underestimation of growth rate and therefore of primary production

We use observations from the Southern Ocean (SO) biogeochemical profiling float array to quantify the meridional pattern of particle export efficiency (PEeff) during the austral productive season. Float estimates reveal a pronounced latitudinal gradient of PEeff, which is quantitatively supported by a compilation of existing ship‐based measurements. Relying on complementary float‐based estimates of distinct carbon pools produced through biological activity, we find that PEeff peaks near the region of maximum particulate inorganic carbon sinking flux in the polar antarctic zone, where net primary production (NPP) is the lowest. Regions characterized by intermediate NPP and low PEeff, primarily in the subtropical and seasonal ice zones, are generally associated with a higher fraction of dissolved organic carbon production. Our study reveals the critical role of distinct biogenic carbon pool production in driving the latitudinal pattern of PEeff in the SO. Plain Language Summary Microbial organisms in seawater transform carbon dioxide into different types of carbon through photosynthesis and food web cycling. These carbon types include particulate and dissolved phases, with particles being more efficiently transferred out of the sunlit ocean via gravitational sinking. The ratio of sinking particulate organic carbon to total organic carbon production, commonly referred to as the particle export efficiency, is a metric used to describe how efficiently carbon moves from the surface to the deep ocean. Using observations from a large array of robots in the Southern Ocean, we find that the different types of biogenic carbon produced control the latitudinal gradient in particle export efficiency, which is highest in regions where particulate inorganic carbon export is greatest, even when photosynthetically fixed carbon is minimal. In other areas where phytoplankton carbon production is moderate but largely comprised of dissolved organic carbon, the particle export efficiency is lower. Key Points Meridional pattern of particle export efficiency (PEeff) estimated from BGC‐Argo aligns with ship‐based observations in the Southern Ocean Low PEeff in subtropical and ice‐covered regions and high PEeff in subpolar regions is linked to the biogenic carbon pools produced Most global models struggle to reproduce the meridional pattern of PEeff in the Southern Ocean

The seasonal variability of phytoplankton vertical distribution is investigated in the South Pacific where observations are scarce and scattered. We used 13 BioGeoChemical‐Argo floats deployed across diverse oceanic environments. The seasonal latitudinal displacement of the Tasman front induces transitions from mesotrophic to oligotrophic conditions. This shift results in Chlorophyll‐a concentration vertical distribution changing from bloom types to Subsurface Chlorophyll Maxima (SCM) types, with intermediate hybrid types between these extremes. Such hybrid profiles frequently occur in the equatorial Pacific, highlighting a large‐scale pattern rather than local island mass effect. In oligotrophic regions, seasonal variations of light availability and stratification dynamics below the mixed layer likely relate SCM to an increase in carbon biomass or photoacclimation. A biomass increase is frequently observed, contrary to previous studies, suggesting that subsurface phytoplankton biomass may have been largely underestimated. This calls for further observations of the water column in these remote undersampled open ocean areas.

Carbon export driven by submesoscale, eddy‐associated vertical velocities (“eddy subduction”), and particularly its seasonality, remains understudied, leaving a gap in our understanding of ocean carbon sequestration. Here, we assess mechanisms controlling eddy subduction's spatial and seasonal patterns using 15 years of observations from BGC‐Argo floats in the Southern Ocean. We identify signatures of eddy subduction as subsurface anomalies in temperature‐salinity and oxygen. The anomalies are spatially concentrated near weakly stratified areas and regions with strong lateral buoyancy gradients diagnosed from satellite altimetry, particularly in the Antarctic Circumpolar Current's standing meanders. We use bio‐optical ratios, specifically the chlorophyll a to particulate backscatter ratio (Chl/bbp) to find that eddy subduction is most active in the spring and early summer, with freshly exported material associated with seasonally weak vertical stratification and increasing surface biomass. Climate change is increasing ocean stratification globally, which may weaken eddy subduction's carbon export potential. Plain Language Summary Oceans play an important role in global climate by soaking up and sequestering atmospheric carbon dioxide. Photosynthetic activity at the surface turns carbon dioxide into organic carbon, and if this carbon leaves the surface to the deep ocean, it can be locked away from the atmosphere. One way this occurs is through the physical circulation associated with swirling eddies, which can rapidly transport organic carbon‐rich surface waters and “inject” them into deep waters. However, we still don't fully understand the seasonal timing of this process, or what drives its spatial distribution. We investigated this in the Southern Ocean, which is very important to global climate, using data collected by drifting robots. We find that this process is the most active in regions where eddies drive strong surface stirring, and during the spring, when weak stratification allows injections to penetrate deep into the ocean. Because this process is poorly represented in climate models, these findings will improve our understanding of how the ocean absorbs carbon. Key Points Eddy subduction in the Southern Ocean is observed as subsurface anomalies in spice and oxygen measured by autonomous profiling floats Spatial distribution is controlled by weak stratification and strong lateral buoyancy gradients, diagnosed using satellite altimetry Bio‐optical proxies suggest that eddy subduction is most active in spring/early summer, driven by weak vertical stratification

Filamentous fungi are one of the most important producers of secondary metabolites. Some of them can havse a toxic effect on the human body, leading to diseases. On the other hand, they are widely used as pharmaceutically significant drugs, such as antibiotics, statins, and immunosuppressants. A single fungus species in response to various signals can produce 100 or more secondary metabolites. Such signaling is possible due to the coordinated regulation of several dozen biosynthetic gene clusters (BGCs), which are mosaically localized in different regions of fungal chromosomes. Their regulation includes several levels, from pathway-specific regulators, whose genes are localized inside BGCs, to global regulators of the cell (taking into account changes in pH, carbon consumption, etc.) and global regulators of secondary metabolism (affecting epigenetic changes driven by velvet family proteins, LaeA, etc.). In addition, various low-molecular-weight substances can have a mediating effect on such regulatory processes. This review is devoted to a critical analysis of the available data on the “turning on” and “off” of the biosynthesis of secondary metabolites in response to signals in filamentous fungi. To describe the ongoing processes, the model of “piano regulation” is proposed, whereby pressing a certain key (signal) leads to the extraction of a certain sound from the “musical instrument of the fungus cell”, which is expressed in the production of a specific secondary metabolite.

Model parameterizations of particulate organic carbon (POC) flux are critical for simulating the strength and future evolution of the biological carbon pump (BCP) but remain poorly constrained because direct observations are sparse. Here, we ask whether the Biogeochemical (BGC)‐Argo proxy observations of POC can help distinguish between these parameterizations by objectively comparing two common parameterizations, which reproduce the observed slowdown of flux attenuation with depth by either decreasing the remineralization rate or increasing the sinking velocity. Both can well reproduce the BGC‐Argo observations in top 1,000 m but predict different POC concentration below, making them possible to be distinguished if BGC‐Argo observations were available there. Therefore, an integration of backscatter sensors into the Deep Argo program is recommended to provide full depth proxy measurements. If the parameterization is known, POC flux can be determined from POC concentration. Thus, the BGC‐Argo proxy observations of POC concentration provide new insights into the BCP. Plain Language Summary Photosynthesis produces organic particles at the ocean's surface. A fraction of these particles sinks to the deep ocean where they are decomposed into inorganic forms. This process, referred to as the biological carbon pump, leads to the storage of inorganic carbon in the deep ocean for hundreds to thousands of years and influences atmospheric CO2 levels. The fraction of organic particles reaching the deep ocean is determined by their remineralization rate and sinking velocity. Both parameters are only poorly constrained by sparse in situ observations of particle flux and climatological data sets of nutrients but are critically important for model projections of future climate. Observation of organic particle concentration throughout the ocean interior is now possible with bio‐optical sensors on Biogeochemical (BGC)‐Argo floats. Particle concentration is dynamically related to vertical particle flux, but has received little attention so far as an observable for calibrating vertical carbon flux in biogeochemical models. This study investigates to what extent the bio‐optical proxy observations of organic carbon concentration can help in calibrating biogeochemical models. Our results suggest that observations of organic carbon concentration can inform us on the appropriate choice of parameterization for particle sinking and provide useful constraints in the calibration of flux‐related parameters. Key Points Two widely used parameterizations of vertical carbon flux are compared objectively in the same model environment The value of Biogeochemical‐Argo observations of backscatter for distinguishing between vertical flux parameterizations is assessed An integration of backscatter sensors into the Deep Argo program will help distinguish between the two parameterizations

Fungal species have the capability of producing an overwhelming diversity of bioactive substances that can have beneficial but also detrimental effects on human health. These so-called secondary metabolites naturally serve as antimicrobial “weapon systems”, signaling molecules or developmental effectors for fungi and hence are produced only under very specific environmental conditions or stages in their life cycle. However, as these complex conditions are difficult or even impossible to mimic in laboratory settings, only a small fraction of the true chemical diversity of fungi is known so far. This also implies that a large space for potentially new pharmaceuticals remains unexplored. We here present an overview on current developments in advanced methods that can be used to explore this chemical space. We focus on genetic and genomic methods, how to detect genes that harbor the blueprints for the production of these compounds (i.e., biosynthetic gene clusters, BGCs), and ways to activate these silent chromosomal regions. We provide an in-depth view of the chromatin-level regulation of BGCs and of the potential to use the CRISPR/Cas technology as an activation tool.

Advanced techniques can accelerate the pace of natural product discovery from microbes, which has been lagging behind the drug discovery era. Therefore, the present review article discusses the various interdisciplinary and cutting-edge techniques to present a concrete strategy that enables the high-throughput screening of novel natural compounds (NCs) from known microbes. Recent bioinformatics methods revealed that the microbial genome contains a huge untapped reservoir of silent biosynthetic gene clusters (BGC). This article describes several methods to identify the microbial strains with hidden mines of silent BGCs. Moreover, antiSMASH 5.0 is a free, accurate, and highly reliable bioinformatics tool discussed in detail to identify silent BGCs in the microbial genome. Further, the latest microbial culture technique, HiTES (high-throughput elicitor screening), has been detailed for the expression of silent BGCs using 500–1000 different growth conditions at a time. Following the expression of silent BGCs, the latest mass spectrometry methods are highlighted to identify the NCs. The recently emerged LAESI-IMS (laser ablation electrospray ionization-imaging mass spectrometry) technique, which enables the rapid identification of novel NCs directly from microtiter plates, is presented in detail. Finally, various trending ‘dereplication’ strategies are emphasized to increase the effectiveness of NC screening.

Abstract Bacterial secondary metabolites (SM) are rich sources of drug leads, and in particular, numerous metabolites have been isolated from actinomycetes. It was revealed by recent genome sequence projects that actinomycetes harbor much more secondary metabolite-biosynthetic gene clusters (SM-BGCs) than previously expected. Nevertheless, large parts of SM-BGCs in actinomycetes are dormant and cryptic under the standard culture conditions. Therefore, a widely applicable methodology for cryptic SM-BGC activation is required to obtain novel SM. Recently, it was discovered that co-culturing with mycolic-acid-containing bacteria (MACB) widely activated cryptic SM-BGCs in actinomycetes. This “combined-culture” methodology (co-culture methodology using MACB as the partner of actinomycetes) is easily applicable for a broad range of actinomycetes, and indeed, 33 novel SM have been successfully obtained from 12 actinomycetes so far. In this review, the development, application, and mechanistic analysis of the combined-culture method were summarized.