Sponge Genus Research Articles

Total Synthesis of the Psammaplysins: Evolution of a Dipolar Cycloaddition Approach

The psammaplysins are a unique group of bromotyrosine-derived natural products isolated from the Psammaplysilla genus of marine sponges. Aside from the various biological activities they possess, synthetic chemists have been drawn to the family for decades due to the intriguing 5/7-spiroisoxazoline-oxepine core common to all members. Herein, we describe our synthetic approach towards the psammaplysin family in the context of this broader work. Our route centers upon the use of a carefully choreographed alkoxymethylenation/1,3-dipolar cycloaddition to construct the key spiroisoxazoline-oxepine ring system, followed by its functionalization and divergent coupling to access various family members. We also detail the development of the first asymmetric approach to this class of marine natural products.

Manzamine A: A Promising Marine-Derived Cancer Therapeutic for Multi-targeted Interactions with E2F8, SIX1, AR, GSK-3β, and V-ATPase - A Systematic Review.

Manzamine A, a natural compound derived from various sponge genera, features a β-carboline structure and exhibits a range of biological activities, including anti-inflammatory and antimalarial effects. Its potential as an anticancer agent has been explored in several tumor models, both in vitro and in vivo, showing effects through mechanisms such as cytotoxicity, regulation of the cell cycle, inhibition of cell migration, epithelial-to-mesenchymal transition (EMT), autophagy, and apoptosis through multi-target interactions of E2F transcriptional factors, ribosomal S6 kinases, androgen receptor (AR), SIX1, GSK-3β, V-ATPase, and p53/p21/p27 cascades. This systematic review evaluates existing literature on the potential application of this marine alkaloid as a novel cancer therapy, highlighting its promising ability to inhibit cancer cell growth while causing minimal side effects.

Sc-SPLASH provides ultra-efficient reference-free discovery in barcoded single-cell sequencing.

Typical high-throughput single-cell RNA-sequencing (scRNA-seq) analyses are primarily conducted by (pseudo)alignment, through the lens of annotated gene models, and aimed at detecting differential gene expression. This misses diversity generated by other mechanisms that diversify the transcriptome such as splicing and V(D)J recombination, and is blind to sequences missing from imperfect reference genomes. Here, we present sc-SPLASH, a highly efficient pipeline that extends our SPLASH framework for statistics-first, reference-free discovery to barcoded scRNA-seq (10x Chromium) and spatial transcriptomics (10x Visium); we also provide its optimized module for preprocessing and k-mer counting in barcoded data, BKC, as a standalone tool. sc-SPLASH rediscovers known biology including V(D)J recombination and cell-type-specific alternative splicing in human and trans-splicing in tunicate (Ciona) and when applied to spatial datasets, detects sequence variation including tumor-specific somatic mutation. In sponge (Spongilla) and tunicate (Ciona), we uncover secreted repeat proteins expressed in immune-type cells and regulated during development; the sponge genes were absent from the reference assembly. sc-SPLASH provides a powerful alternative tool for exploring transcriptomes that is applicable to the breadth of life's diversity.

Leptilostis, a replacement name for Tetillopsis Hong, 1982 (Coleoptera: Curculionidae), junior homonym of Tetillopsis Schrammen, 1910 (Porifera: Tetillidae)

Schrammen (1910) described a genus of fossil tetillid sponge, naming it Tetillopsis Schrammen, 1910, and described two species from north-western Germany, viz., T. doeringi Schrammen and T. longitridens Schrammen. Tetillopsis doeringi was later designated as the type species of the genus (de Laubenfels, 1955); and this name is still used in current taxonomic practice (https://paleobiodb.org/classic/basicTaxonInfo?taxon_no=2987 The Paleobiology Database 2024).

Sponge Spicules in Sediments: A Proxy for Past and Present Sponge Fauna Assessment in Ha Long Bay (Vietnam)

The study of cryptic sponges can be challenging, as they are difficult to detect in the environment without the use of destructive methods. The permanence of mineral skeletal components of Porifera in sediments is therefore a tool that can provide support for a more comprehensive study of sponge fauna. In this context, sediments collected from four karst lakes in Ha Long Bay (Vietnam), plus two surrounding sea areas, were processed to extract spicules belonging to sponges with siliceous skeletons. From the morphology of the spicules, it was possible to trace the taxa of the sponges present in the area at that time or earlier. It was found that each lake had a sponge fauna composition characterized by different families and genera. Moreover, sponge taxa identified in the surrounding sea areas differed significantly from the ones inside of the neighboring lakes. In addition, it was possible to identify the presence of four sponge genera not yet recorded in the South China Sea area. Thus, the study of spicules trapped in sediments proved to be a useful tool for a comprehensive study of sponge fauna.

Sycetta papillata sp. nov. (Porifera, Calcarea): the first record of Sycetta to the Southwestern Atlantic Ocean.

Sycetta is a poorly known genus of calcareous sponges, primarily distinguished by the presence of tubes (the choanocyte chambers) radially organized around the atrial cavity and completely separated from each other. These tubes, referred to as conical diverticula or more aptly as papillae, impart a distinctive appearance to the external morphology of the sponges. Herein, we present the description of Sycetta papillata sp. nov., based on the examination of specimens collected several decades ago in the state of Bahia, located in Northeastern Brazil. The presence of a single category of diactines and atrial region formed exclusively by tetractines makes this species unique within the genus. While some species of Sycetta have been documented in deep regions, exceeding depths of 200 meters, the distribution range of S. papillata sp. nov. spans from 0.5 to 25 meters in depth. A comparative table of Sycetta species is being provided.

A new Acanthotetilla sponge from the Southwest Atlantic (Tetillidae, Spirophorina, Tetractinellida, Demospongiae), with an updated discussion on the diversity, distribution and morphologic characters of Acanthotetilla spp.

Acanthotetilla is a genus of tetillid sponges diagnosed by the presence of medium-sized, heavily spined oxeas, which are known as megacanthoxeas (or simply acanthoxeas). Currently, seven species are known worldwide: three from the Western Atlantic (A. gorgonosclera, A. rocasensis and A. walteri), three from the Western Indian (A. hemisphaerica, A. enigmatica and A. seychellensis) and one from the Western Pacific (A. celebensis). A megacanthoxea-bearing specimen was obtained from the Fernando de Noronha Archipelago, Southwest Atlantic, in 2016. It is described here as a new Acanthotetilla, namely, A. noronhensis sp. nov. This new species has two categories of megacanthoxeas, like A. celebensis from Celebes/Sulawesi Sea, Indonesia. However, the former differs from the latter, as well as from other congeners, by the combination of endolithic habit and spiculation. Acanthotetilla noronhensis sp. nov. is known on the basis of a single specimen from a large collection of sponges from Fernando de Noronha. Besides, the species was not found in other sponge collections from different areas of Brazil, including oceanic areas. Thus, the new species has probably a low abundance and restricted distribution, alike all other known Acanthotetilla species, aside A. celebensis, which (regardless its low abundance) occurs in a large sector of the western Pacific. Despite A. noronhensis sp. nov. and A. celebensis being separated by a wide geographic distance, the unique occurrence of two categories of megacanthoxeas might suggest closer phylogenetic relationship and biogeographic history as well. A wider discussion on the diversity, distribution and morphologic characters of Acanthotetilla spp. is supplied in this study. A comparative taxonomic table and a taxonomic identification key to Acanthotetilla spp. is supplied as well.

A new sponge genus from the Chengjiang biota with an intriguing combination of skeletal characters

The development of fossil sponge systematics is hindered by factors such as their low anatomical complexity and the low preservation potential of many characters used in the definition of extant sponge clades. Here we describe Calliospongia chunchengia gen. et sp. nov., a new sponge from the Lower Cambrian Chengjiang biota, which possesses a unique combination of characters. The skeleton of C. chunchengia is similar to those of leptomitid protomonaxonids in being composed of large spicules arranged longitudinally. However, it is distinct enough to belong in its own genus and even question a leptomitid affinity, because, unlike the members of this group, which usually have two categories of diactine spicules, its skeleton is entirely composed of triactines. The new taxon shares the presence of large megascleres with demosponges, hexactinellids and the ascosponges, suggesting an affinity to the total group of Silicea. It is also reminiscent of the hexactinellid-like reticulosans, showing a potential connection between two major types of Early Palaeozoic sponge body plans. A more accurate definition of the Cambro-Ordovician groups and the creation of a total evidence framework that integrates extinct and extant sponge morphology into the phylogenetic scenario derived from phylogenomics seem to be essential steps for the improvement of our understanding of early sponge evolution.

Front Cover: Anti‐Inflammatory Effects of New Naphthyridine from Sponge Aaptos suberitoides in LPS‐Stimulated RAW 264.7 Macrophages via Regulation of MAPK and Nrf2 Signaling Pathways (Chem. Biodiversity 6/2023)

Chemistry & BiodiversityEarly View e202300701 Cover PictureFree Access Anti-Inflammatory Effects of New Naphthyridine from Sponge Aaptos suberitoides in LPS-Stimulated RAW 264.7 Macrophages via Regulation of MAPK and Nrf2 Signaling Pathways First published: 19 May 2023 https://doi.org/10.1002/cbdv.202300701AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Graphical Abstract Front Cover. Two new naphthyridine compounds, 4-methoxycarbonyl-5-oxo-1,6-naphthyridine (1) and 5-methoxycarbonyl-4-oxo-1,6-naphthyridine (2), were isolated from the MeOH extracts of sponge, Aaptos suberitoides, collected in South Sea, China. Their structures were determined by spectroscopic methods. And the structure of compound 1 was further confirmed via single crystal X-ray diffraction analysis. This is the first report of an anti-inflammatory compound isolated from the sponge genus Aaptos. Biological assays and mechanism research have found that compound 1 can significantly inhibited the production of NO in RAW264.7 cells stimulated by LPS, and exerted anti-inflammatory effects by activating Nrf2/HO-1 and inhibiting MAPK signaling pathways as presented by Meng-Shan Liu et al. in their research article at 10.1002/cbdv.202300410. Early ViewOnline Version of Record before inclusion in an issuee202300701 RelatedInformation

Microbiome diversity from sponges biogeographically distributed between South America and Antarctica

Sponges from South America and Antarctica are evolutionarily closely related. Specific symbiont signatures that could differentiate these two geographic regions are unknown. This study aimed to investigate the microbiome diversity of sponges from South America and Antarctica. In total 71 sponge specimens were analyzed (Antarctica: N = 59, 13 different species; South America: N = 12, 6 different species). Illumina 16S rRNA sequences were generated (2.88 million sequences; 40K ± 29K/sample). The most abundant symbionts were heterotrophic (94.8 %) and belonged mainly to Proteobacteria and Bacteroidota. EC94 was the most abundant symbiont and dominated the microbiome of some species (70–87 %), comprising at least 10 phylogroups. Each of the EC94 phylogroups was specific to one genus or species of sponge. Furthermore, South America sponges had higher abundance of photosynthetic microorganisms (2.3 %) and sponges from Antarctica, the highest abundance of chemosynthetic (5.5 %). Sponge symbionts may contribute to the function of their hosts. The unique features from each of these two regions (e.g., light, temperature, and nutrients) possibly stimulate distinct microbiome diversity from sponges biogeographically distributed across continents.

Terpene biosynthesis in marine sponge animals

Sea sponges are the largest marine source of small-molecule natural products described to date. Sponge-derived molecules, such as the chemotherapeutic eribulin, the calcium-channel blocker manoalide, and antimalarial compound kalihinol A, are renowned for their impressive medicinal, chemical, and biological properties. Sponges contain microbiomes that control the production of many natural products isolated from these marine invertebrates. In fact, all genomic studies to date investigating the metabolic origins of sponge-derived small molecules concluded that microbes-not the sponge animal host-are the biosynthetic producers. However, early cell-sorting studies suggested the sponge animal host may play a role particularly in the production of terpenoid molecules. To investigate the genetic underpinnings of sponge terpenoid biosynthesis, we sequenced the metagenome and transcriptome of an isonitrile sesquiterpenoid-containing sponge of the order Bubarida. Using bioinformatic searches and biochemical validation, we identified a group of type I terpene synthases (TSs) from this sponge and multiple other species, the first of this enzyme class characterized from the sponge holobiome. The Bubarida TS-associated contigs consist of intron-containing genes homologous to sponge genes and feature GC percentage and coverage consistent with other eukaryotic sequences. We identified and characterized TS homologs from five different sponge species isolated from geographically distant locations, thereby suggesting a broad distribution amongst sponges. This work sheds light on the role of sponges in secondary metabolite production and speaks to the possibility that other sponge-specific molecules originate from the animal host.

Callyspongia spp.: Secondary Metabolites, Pharmacological Activities, and Mechanisms

One of the most widespread biotas in the sea is the sponge. Callyspongia is a sponge genus found in the seas, making it easily available. In this review, the pharmacological activity and mechanism of action of the secondary metabolites of Callyspongia spp. are addressed, which may lead to the development of new drugs and targeted therapeutic approaches. Several scientific databases, such as Google Scholar, PubMed, ResearchGate, Science Direct, Springer Link, and Wiley Online Library, were mined to obtain relevant information. In the 41 articles reviewed, Callyspongia spp. was reported to possess pharmacological activities such as cytotoxicity against cancer cell lines (36%), antifungal (10%), anti-inflammatory (10%), immunomodulatory (10%), antidiabetic and antiobesity (6%), antimicrobial (8%), antioxidant (4%), antineurodegenerative (4%), antihypercholesterolemic (2%), antihypertensive (2%), antiparasitic (2%), antiallergic (2%), antiviral (2%), antiosteoporotic (2%), and antituberculosis (2%) activities. Of these, the antioxidant, antituberculosis, and anti-inflammatory activities of Callyspongia extract were weaker compared with that of the control drugs; however, other activities, particularly cytotoxicity, show promise, and the compounds responsible may be developed into new drugs.

Novel trends of genome evolution in highly complex tropical sponge microbiomes

BackgroundTropical members of the sponge genus Ircinia possess highly complex microbiomes that perform a broad spectrum of chemical processes that influence host fitness. Despite the pervasive role of microbiomes in Ircinia biology, it is still unknown how they remain in stable association across tropical species. To address this question, we performed a comparative analysis of the microbiomes of 11 Ircinia species using whole-metagenomic shotgun sequencing data to investigate three aspects of bacterial symbiont genomes—the redundancy in metabolic pathways across taxa, the evolution of genes involved in pathogenesis, and the nature of selection acting on genes relevant to secondary metabolism.ResultsA total of 424 new, high-quality bacterial metagenome-assembled genomes (MAGs) were produced for 10 Caribbean Ircinia species, which were evaluated alongside 113 publicly available MAGs sourced from the Pacific species Ircinia ramosa. Evidence of redundancy was discovered in that the core genes of several primary metabolic pathways could be found in the genomes of multiple bacterial taxa. Across hosts, the metagenomes were depleted in genes relevant to pathogenicity and enriched in eukaryotic-like proteins (ELPs) that likely mimic the hosts’ molecular patterning. Finally, clusters of steroid biosynthesis genes (CSGs), which appear to be under purifying selection and undergo horizontal gene transfer, were found to be a defining feature of Ircinia metagenomes.ConclusionsThese results illustrate patterns of genome evolution within highly complex microbiomes that illuminate how associations with hosts are maintained. The metabolic redundancy within the microbiomes could help buffer the hosts from changes in the ambient chemical and physical regimes and from fluctuations in the population sizes of the individual microbial strains that make up the microbiome. Additionally, the enrichment of ELPs and depletion of LPS and cellular motility genes provide a model for how alternative strategies to virulence can evolve in microbiomes undergoing mixed-mode transmission that do not ultimately result in higher levels of damage (i.e., pathogenicity) to the host. Our last set of results provides evidence that sterol biosynthesis in Ircinia-associated bacteria is widespread and that these molecules are important for the survival of bacteria in highly complex Ircinia microbiomes.2qsxhK4E14RHhUQ45Lc7ZoVideo

A European nudibranch new to the Gulf of Maine: Doris pseudoargus Rapp, 1827

The Gulf of Maine (GOM) has seen an increasing number of introduced species, some of which have significantly impacted benthic community structure. In 2017, a number of specimens of the European dorid nudibranch, Doris pseudoargus, were observed on rocky ledges in waters off Cape Ann, Massachusetts. The presence of numerous specimens and egg masses suggested the species had been established before 2017. Additional field observations and literature searches revealed specimens occurring from Nova Scotia to the northern end of the Cape Cod Canal, which poses the question, when and where did the initial introduction take place and how? Genetic analysis confirmed the species as Doris pseudoargus with genomic similarities to specimens from Northern Europe. Until this introduction, the GOM had only one species of sponge feeding nudibranch, Cadlina laevis, which is a trophic specialist on one genus of sponge. Unlike this endemic, stenotrophic feeding dorid, the introduction of another large sized, sponge predator known to feed on diverse sponge species, that occur from the intertidal to at least 25 m in depth has the potential to significantly impact community structure over a wide variety of hard bottom habitats.

Leucotreton kurilense, a new genus and species of calcareous sponges of the family Sycanthidae (Porifera: Calcarea: Leucosolenida) from the northwestern Pacific Ocean, with contribution to taxonomy and nomenclature of related genera

A calcareous sponge Leucotreton kurilense gen. et sp. nov. (Sycanthidae) is described from the area of the Kuril Islands. It differs from all members of the family Sycanthidae in its aquiferous system, which is intermediate between leuconoid and sylleibid. Taxonomic status and nomenclature of several taxa formerly assigned to Sycanthidae is discussed. It is shown that the genus Dermatreton Jenkin, 1908 does not belong to Sycanthidae but this name is a senior synonym of Breitfussia Borojevic et al., 2000 (Jenkinidae), syn. nov.; Dermatreton contains three species previously included in Breitfussia: D. chartaceum Jenkin, 1908, D. schulzei (Breitfuss, 1896), comb. nov. and D. vitiosum (Brøndsted, 1931), comb. nov. It is shown that Tenthrenodes Jenkin, 1908 should be considered as a junior synonym of Sycon Risso, 1827, syn. nov. A new genus Scytotreton gen. nov. (Sycanthidae) is created to accommodate two species originally described in the genera Dermatreton and Tenthrenodes, respectively: Scytotreton hodgsoni (Jenkin, 1908), comb. nov. and S. scotti (Jenkin, 1908), comb. nov.

Two New Species and One New Genus of Glass Sponges (Hexactinellida: Euplectellidae and Euretidae), From a Transect on a Seamount in the Northwestern Pacific Ocean

Hexactinellid sponges often form structural habitats for other organisms and thus support high biodiversity. Two representative morphotypes of hexactinellid sponges were sampled by a remotely operated vehicle along a transect (depths of 2377–2758 m) on the Ko-Hakucho Guyot in the northwestern Pacific Ocean, both new to science. One new species,Flavovirens hemiglobusgen. et sp. nov., which is pedunculate and bears the main choanosomal spicules of diactins, is clearly attributed to the euplectellid subfamily Bolosominae. Its set of microscleres present (namely, predominating oxyhexasters and discasters, and rare discohexasters and staurodiscs) characterizes it as a new genus. The other new species,Chonelasma tyloscopulatumsp. nov., which is funnel in form without dichotomous branching tubes or lateral oscula and has firm body walls supported by a three-layered dictyonal framework, is clearly attributed to the euretid genusChonelasma(subfamily Chonelasmatinae). Its presence of surface pentactins, two types of scopules, and both oxy- and disco-tipped hexasters or hemihexasters as common microscleres, characterizes it as a new species. The placements are also supported by molecular phylogenetic evidence from nuclear 18S rDNA and 28S rDNA, and mitochondrial 16S rDNA and cytochrome c oxidase subunit I (COI) gene. More sampling efforts should be conducted to improve the understanding of the biodiversity of deep-sea seamount sponges.

Significance of fish–sponge interactions in coral reef ecosystems

Sponges (Porifera) are a key component of many coral reef ecosystems. In some biogeographic regions, they are considered the dominant benthic fauna and they have the capacity to fulfil many similar roles to reef-building scleractinians. Certainly, sponges predominate at depth, below the critical thresholds of most coral species. The biological and physical attributes of these biogenic communities contribute essential resources for many reef-associated fishes. However, while fish–sponge interactions have been widely documented, there is no global synthesis of the literature on these interrelationships from the perspective of fish ecology. Here we evaluate coral reef fish–sponge relationships, including the role of sponges in providing food and shelter for fishes, the influence fishes have on sponge distribution and abundance and possible outcomes of climate change on fish–sponge interactions. To date, 16 fish families have been shown to associate with 56 different sponge genera, using them as either a source of shelter (n = 17) or a food source (n = 50), although methodologies for the latter currently lack consistency. We demonstrate that a more comprehensive understanding of fish–sponge interactions has been garnered from tropical Atlantic coral reefs, which has resulted in a strong biogeographic bias. While it is evident that in some areas of the Caribbean fish are key in shaping the distribution and abundance of sponges, it is not yet known whether this conclusion applies to the Indo-Pacific. With increasing stresses such as bleaching events impacting coral reef ecosystems, further work is needed to evaluate whether sponges can fulfil similar functional roles to those previously provided by reef-building scleractinians. Similarly, determining whether sponge expansion will compensate for the negative effects of reef degradation, or contribute to their decline, is vital.

Biodiversity of the Indonesian marine sponge genus Aaptos with molecular networking approach

Many natural products have been isolated from the cryptic species of the Indonesian marine sponge. Despite this, it remains unclear how sponges produce such a diverse array of metabolites and their relationship to sponge diversity. During our expedition in 2017-2019, we collected the Indonesian marine sponge of the genus Aaptos, which was found surrounding Weh and Aceh Islands, the northwesternmost part of the Indonesian archipelago. All specimens were subjected to a feature-based molecular networking approach to understand their relationship. The molecular phylogenetic clades of genus Aaptos were examined by cytochrome oxide I (COI) while the presence of their chemotypes were confirmed by chemical analysis based on bioassay-guided separation with several steps of chromatography. As results, the presence Aaptos suberitoides, Aaptos aaptos, Aaptos nigra, Aaptos lobata, and Aaptos sp. were confirmed by the molecular phylogenetic. On the other hand, chemical analysis showed the presence of alkaloid-class molecules on all specimens. Interestingly, feature-based molecular networking revealed the whole figure of cryptic species were formed a clear and distinct group together with their chemotypes. Consequently, it confirmed that the relationship between the presence of each species as well as its chemotype can be distinguished clearly. In conclusion, we suspect the chemical analysis of the genus Aaptos have unknowingly conflated between different cryptic species, resulting in the seemingly idiosyncratic chemical variations.

Unique spicules may confound species differentiation: taxonomy and biogeography of Melonanchora Carter, 1874 and two new related genera (Myxillidae: Poecilosclerida) from the Okhotsk Sea.

Sponges are amongst the most difficult benthic taxa to properly identify, which has led to a prevalence of cryptic species in several sponge genera, especially in those with simple skeletons. This is particularly true for sponges living in remote or hardly accessible environments, such as the deep-sea, as the inaccessibility of their habitat and the lack of accurate descriptions usually leads to misclassifications. However, species can also remain hidden even when they belong to genera that have particularly characteristic features. In these cases, researchers inevitably pay attention to these peculiar features, sometimes disregarding small differences in the other “typical” spicules. The genus Melonanchora Carter, 1874, is among those well suited for a revision, as their representatives possess a unique type of spicule (spherancorae). After a thorough review of the material available for this genus from several institutions, four new species of Melonanchora, M. tumultuosa sp. nov., M. insulsa sp. nov., M. intermedia sp. nov. and M. maeli sp. nov. are formally described from different localities across the Atlanto-Mediterranean region. Additionally, all Melonanchora from the Okhotsk Sea and nearby areas are reassigned to other genera; Melonanchora kobjakovae is transferred to Myxilla (Burtonanchora) while two new genera, Hanstoreia gen. nov. and Arhythmata gen. nov. are created to accommodate Melonanchora globogilva and Melonanchora tetradedritifera, respectively. Hanstoreia gen. nov. is closest to Melonanchora, whereas Arhythmata gen. nov., is closer to Stelodoryx, which is most likely polyphyletic and in need of revision.

RSK1 vs. RSK2 Inhibitory Activity of the Marine β-Carboline Alkaloid Manzamine A: A Biochemical, Cervical Cancer Protein Expression, and Computational Study.

Manzamines are complex polycyclic marine-derived β-carboline alkaloids with reported anticancer, immunostimulatory, anti-inflammatory, antibacterial, antiviral, antimalarial, neuritogenic, hyperlipidemia, and atherosclerosis suppression bioactivities, putatively associated with inhibition of glycogen synthase kinase-3, cyclin-dependent kinase 5, SIX1, and vacuolar ATPases. We hypothesized that additional, yet undiscovered molecular targets might be associated with Manzamine A’s (MZA) reported pharmacological properties. We report here, for the first time, that MZA selectively inhibited a 90 kDa ribosomal protein kinase S6 (RSK1) when screened against a panel of 30 protein kinases, while in vitro RSK kinase assays demonstrated a 10-fold selectivity in the potency of MZA against RSK1 versus RSK2. The effect of MZA on inhibiting cellular RSK1 and RSK2 protein expression was validated in SiHa and CaSki human cervical carcinoma cell lines. MZA’s differential binding and selectivity toward the two isoforms was also supported by computational docking experiments. Specifically, the RSK1-MZA (N- and C-termini) complexes appear to have stronger interactions and preferable energetics contrary to the RSK2–MZA ones. In addition, our computational strategy suggests that MZA binds to the N-terminal kinase domain of RSK1 rather than the C-terminal domain. RSK is a vertebrate family of cytosolic serine-threonine kinases that act downstream of the ras-ERK1/2 (extracellular-signal-regulated kinase 1/2) pathway, which phosphorylates substrates shown to regulate several cellular processes, including growth, survival, and proliferation. Consequently, our findings have led us to hypothesize that MZA and the currently known manzamine-type alkaloids isolated from several sponge genera may have novel pharmacological properties with unique molecular targets, and MZA provides a new tool for chemical-biology studies involving RSK1.