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. 2026 Feb 25;11(9):14797–14805. doi: 10.1021/acsomega.5c11024

Fragment-Based Online OzESI-MS, NMR, and Computational DP4+/DFT Approaches to the Characterization of the Putative Biosynthetic Lipid Precursor of Atkamine from Alaskan Latrunculia Sponges

Menny M Benjamin †, Cody F Dickinson †, Jared S Wood ‡, R Thomas Williamson ‡, George S Hanna §, Ahmed S Alford †, Robert P Stone ∥, Gerald R Hoff ⊥, Abhi R Samala †, Fayaj A Mulani #, Qibin Zhang #,∇, Mark T Hamann †,*
PMCID: PMC12980237  PMID: 41835544

Abstract

The extraction of Latrunculia sponges collected along the coast of the Aleutian Islands of Alaska yielded a lipid fraction, in which a natural long-chain monounsaturated aldehyde, (Z)-docos-15-enal (1), was isolated for the first time from this genus of sponge. Experimental, DP4+/DFT structure-probability calculations, and ab initio NMR chemical shift (CS) computational data comparing (Z)-docos-15-enal isolated from a natural sponge source with the previously reported synthetic material, confirmed the cis (Z) configuration of the double bond. Online ozonolysis LC-ESI-MS (OzESI) data validated the assignment of the C-15/C-16 olefin along the lipid chain. Aldehyde-based metabolites may serve as biosynthetic precursors for complex lipid alkaloids such as the atkamine pyrroloiminoquinone (PIQ).

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Introduction

The Bering Sea and Aleutian Islands boast one of the world’s most productive fisheries and are supported by diverse populations of commercially important bottom-dwelling finfish and shellfish. While that productivity may be threatened by climate change, scientists continue to discover substantial numbers of new invertebrate species in this unique high-latitude marine environment. , Polar invertebrates have a rich history of producing bioactive secondary metabolites, which play vital ecological roles for bottom-dwelling and sessile organisms. − As part of the groundfish assessment surveys conducted by the National Oceanic and Atmospheric Administration (NOAA) Alaska Fisheries Science Center (AFSC), sponges of the genus Latrunculia were collected as bycatch to investigate the unique chemistry and bioactivities of their secondary metabolites.

Latrunculia sponges are known for their chemically diverse and bioactive pyrroloiminoquinone (PIQ) alkaloids, including, but not limited to, the aleutianamines, discorhabdins, makaluvamines, and tsitsikammamines, which exhibit cytotoxic, antimicrobial, antiviral, and antiprotozoal activities. − For example, aleutianamine, originally isolated from Latrunculia austini, is reported to be a solid tumor-selective alkaloid with an IC50 of 25 nM in PANC-1 cells. In addition to their broad bioactivities, interest in the challenge of constructing complex ring systems in the PIQ class has led to numerous total syntheses. − Many of these syntheses are inspired by proposed biosynthetic pathways involving discorhabdin-related alkaloids and indolamines, such as citharoxazole and tryptamine, respectively. ,−

Herein, we report the isolation and characterization of a long-chain monounsaturated aldehyde, (Z)-docos-15-enal (1), from Latrunculia oparinae and L. hamanni sponges, via experimental, DP4+/DFT structure-probability calculations, and ab initio NMR chemical shift (CS) computational data comparing compound 1 isolated from a natural sponge source and the previously reported synthetic material used in synthetic studies toward atkamine by Zhang et al. The placement of the double bond was validated by the characteristic ozonolysis product ions of the fragmented lipid chain.

Atkamine is the only PIQ that bears a monounsaturated lipid side chain, along with a cyclic ether (Figure ). − We have previously discussed the potential of a monounsaturated fatty acid precursor as a core building block of atkamine, along with the amino acid scaffolds tyrosine and tryptophan. Hence, in addition to that work, we propose a mechanism for the transformation of compound 1 into the (Z)-docos-15-enoyl-CoA intermediate and discuss an alternative biogenesis pathway via an α-thiolated aldehyde intermediate.

1.

1

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Chemical structures of atkamine and its putative lipid aldehyde precursor, (Z)-docos-15-enal (1).

Results and Discussion

Extraction and Purification

Sponges were collected off the coast of the Aleutian Islands, Alaska, as bycatch from chartered fishing trawler vessels during NOAA’s groundfish assessment survey (Figure ). The use of sponges recovered as bycatch provides a sustainable way to obtain research samples that would otherwise be discarded at sea. Lipids were extracted from the sponges with nonpolar organic solvents and were subsequently extracted with 100% ethanol (EtOH). The crude EtOH extract was fractionated by flash silica gel chromatography using mixtures of dichloromethane (DCM) and methanol (MeOH). The DCM forerun was subjected to additional flash silica gel chromatography, yielding compound 1 (see the Experimental Section).

2.

2

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Collection sites of L. oparinae and L. hamanni sponges during the NOAA AFSC 2024 Groundfish Assessment Survey of the Aleutian Islands, Alaska. Points: green (L. oparinae), purple (L. hamanni), and gray (both species). The haul data for the vessels, FV Ocean Explorer (OEX) and FV Alaska Provider (AKP), are available in Table S4. Map data: © Google Earth (Google; 2025 Maxar Technologies, SIO, NOAA, U.S. Navy, NGA, Landsat/Copernicus); ROV image of submerged Latrunculia sponges: © Robert P. Stone (NOAA, AFSC).

Spectroscopic Characterization

The 1H NMR spectrum (CDCl3, 600 MHz) for compound 1 exhibited proton signals characteristic of an aldehyde at δ 9.78 ppm (t, J = 1.9 Hz, 1H), α-methylene vicinal protons at δ 2.43 ppm (td, J = 1.9, 7.4, 2H), olefinic protons at δ 5.40 – 5.34 ppm (m, 2H), allylic methylene protons at δ 2.07 – 2.00 ppm (m, 4H), and terminal methyl protons at δ 0.90 ppm (t, J = 7.0 Hz, 3H) (Figure S1). The 13C NMR spectrum (CDCl3, 600 MHz) for compound 1 exhibited signals characteristic of carbonyl at δ 203.0 ppm, olefinic carbons at δ 129.9 ppm (overlapped signals), allylic methylene carbons at δ 27.22 and 27.21 ppm, and a terminal methyl carbon at δ 14.1 ppm (Figure S2). Analysis of the 1H and 13C NMR spectra provided evidence that the carbonyl group was not conjugated. Specifically, the multiplicity and J-based analysis of the aldehyde proton resonance at δ 9.78 ppm (t, J = 1.9 Hz) and the carbonyl carbon resonance at δ 203.0 ppm support this assignment.

The HMBC NMR spectrum (CDCl3, 600 MHz) for compound 1 provided additional evidence of a long-chain monounsaturated aldehyde (Figure S3). H-2 (δ 2.43) correlated with C-3 (δ 22.1), and H-4 (δ 1.28) correlated with C-5 (δ 29.7), establishing an α-methylene within the aliphatic chain. H-15 (δ 5.36) correlated with C-14 (δ 27.3), supporting an allylic methylene. Correlations from H-14/H-17 (δ 2.02) to C-13/C-18 (δ 29.5) and to C-15/C-16 (δ 130.0) further defined the allylic and vinyl-carbons, respectively, surrounding the olefin region. Finally, H-22 (δ 0.90) showed an HMBC correlation to C-21 (δ 22.7), confirming their connectivity at the terminus of the chain. An HMBC correlation map for compound 1 is shown below (Figure ).

3.

3

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HMBC correlations of compound 1.

The experimental 1H, 13C, and HMBC NMR spectroscopic data comparing the natural and synthetic versions of compound 1, as well as atkamine, are listed in Table . As can be seen below, the allylic C-14 and C-17 signals (δ 27.22 and 27.21 ppm) of compound 1 closely align with the synthetic aldehyde, δ 27.3 ppm (overlapped signals), as well as with the allylic C-36 and C-39 signals (δ 26.9 and 27.0 ppm) reported for atkamine in its aliphatic side chain. , In addition, the matching signals observed in the stacked 1H and 13C NMR spectra for compound 1 (natural vs synthetic) strongly support the structural elucidation, including the Z configuration and the position of the alkene within the lipid chain (Figures S4 and S5).

1. Experimental 1H and 13C NMR Spectroscopic Data (δ ppm) for the Aldehyde (Natural vs Synthetic) vs. Atkamine.

  natural aldehyde (1)
 synthetic aldehyde
 atkamine
position δC, type δH, (mult., J in Hz) δC, type δH, (mult., J in Hz) position δC, type δH, (mult., J in Hz)
1 203.0, C 9.78 (1H, t, 1.9) 202.8, C 9.73 (1H, t, 1.9) – – –
2 43.9, CH2 2.43 (2H, td, 7.4, 1.9) 44.0, CH2 2.37 (2H, td, 7.4, 1.9) – – –
3 22.1, CH2 1.64 (2H, m) 22.2, CH2 1.60 (2H, m) – – –
4–13, 18–21 31.79, 29.9 29.78, 29.75, 29.65, 29.64, 29.58, 29.56, 29.43, 29.36, 29.32, 29.18, 29.18, 22.7, CH2 chain 1.28 (28H, m) 31.9, 29.9, 29.8, 29.7, 29.3, 29.1, 22.8, CH2 chain 1.28 (28H, m) 28–35, 40–43 29.5–28.5, 25.9 CH2 1.3 (28H, m)
14, 17 27.22, 27.21, CH2 2.02 (4H, m) 27.3 27.3, CH2 2.0 (4H, m) 36, 39 26.9, 27.0, CH2 1.95 (4H, m)
15, 16 129.9 (overlapped), CH 5.36 (2H, m) 130.0 (overlapped), CH 5.33 (2H, m) 37, 38 130.06, 130.04, CH 5.29 (2H, dt, 9.3, 10.8)
22 14.1, CH3 0.90 (3H, t, 7.0) 14.2, CH3 0.88 (t, J = 7.1 Hz, 3H) 44 14.3, CH3 0.81 (3H, t)
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a

Measured at 150 MHz in CDCl3.

b

Measured at 600 MHz in CDCl3.

c

Measured at 400 MHz in CDCl3.

d

Measured at 100 MHz in CDCl3.

e

Measured in DMSO-d 6.

Online ozonolysis LC-ESI-MS (OzESI) with a high-resolution Orbitrap mass spectrometer was used to determine the position of the CC double bond, as reported previously. − Compound 1 eluted at 11.6 min, expected for a long-chain monounsaturated aliphatic aldehyde under a lipidomics LC gradient conditions, with a unique adduct ion [M + NH4–H2O]+, at m/z 322.3466. Under online ozonolysis conditions, new fragment ions with m/z of 240.2318, 241.2157, and 258.2425 were generated and coeluted with the precursor ion, corresponding to the aldehyde product ions, [M + NH4–H2O]+, [M + H]+, and [M + NH4]+, respectively, that resulted from the n-7 neutral loss upon reaction with ozone (Figure S6). The ion assignments were confirmed with a mass measurement accuracy calculation, all within 2 ppm (Figure S7).

Computational NMR CS Predictions and DP4+/DFT Calculations

The allylic methylene carbon signals at δ 27.22 and 27.21 ppm for C-14 and C-17, respectively, align with ChemDraw ab initio NMR CS 13C prediction data of δ 27.7 for an alkene in the (Z)-configuration (Figure S8 and Table S1). These chemical shifts support the presence of an aliphatic, long-chain monounsaturated aldehyde and are consistent with those reported by Zhang et al. In addition, DP4+/DFT structure-probability calculations were performed on 20 different conformations (the lowest-energy and most diverse) for each configuration using the B3LYP and mPW1PW91 functionals for a total of 80 calculations. As a result, compound 1 was assigned a 100% probability of possessing the (Z)-configuration for each set of calculations (Figure and Tables S2 and S3). DFT calculations cannot reliably distinguish between structures with alternative CC placements.

4.

4

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DP4+ outcome for (E)-docos-15-enal (Isomer 1) and (Z)-docos-15-enal (Isomer 2). DFT calculations at the PCM-mPW1PW91/6–311 + G­(d,p)//B3LYP/6–31 + G­(d) and PCM-B3LYP/6–311 + G­(d,p)//B3LYP/6–31 + G­(d) levels of theory were used for the analysis.

While the stereochemistry of atkamine was assigned using NMR correlations, ECD, and DFT modeling, its monounsaturated fatty acid side chain was determined solely by MS and computational comparisons of allylic carbons to assign configuration. In contrast, the independent, simpler aldehyde precursor enabled a lipid-fragment-based computational DP4+/DFT approach, providing direct statistical validation of the (Z)-configuration of the alkene. This demonstrates the utility of DP4+/DFT structure-probability calculations to verify the configuration of precursor intermediates or fragments for the structural elucidation of complex natural products such as atkamine.

Proposed Biogenesis of Atkamine

Biomimetic syntheses have been reported involving indole derivatives and thioester fatty acids (activated by acyl-CoA synthetases), as well as indolamines and aldehydes. ,, For instance, the β-carboline core found in manzamines from the genus Acanthostrongylophora of Indonesian sponges has been synthesized via a Pictet-Spengler reaction between tryptamine and an aldehyde electrophile, a reaction closely related to the putative biosynthetic pathway for atkamine and a key step in earlier proposed biosynthetic routes to manzamine. − The composition of cold-water Latrunculia lipid extracts is reported to be rich in unusual, long-chain unsaturated fatty acids, which have demonstrated antioxidant activity and the potential to scavenge free radicals. Given this fact, it is likely that, in Latrunculia and other genera of polar sponges, lipid metabolism naturally reduces fatty acids to aldehydes via fatty acyl reductases. ,

We previously proposed the biogenesis of atkamine via the acylation of the acyl-CoA aldehyde to brominated makaluvamine M, followed by a series of oxidation–reduction, addition, cleavage, and cyclization reactions. Hence, we propose the preceding steps for converting compound 1 into an enzymatically activated acyl-CoA product, which would react with 18-Br makaluvamine M (2) to form the monounsaturated fatty acid chaina core component of atkamine. As illustrated in Scheme , compound 1 is oxidized to the fatty acid (Z)-docos-15-enoic acid (1a) via aldehyde dehydrogenase (ALDH). Next, the fatty acid is converted to (Z)-docos-15-enoyl-CoA (1b) via adenylation and thioesterification by an acyl-CoA synthetase. An activated (Z)-docos-15-enoyl-CoA possesses a thioester with an electrophilic carbonyl group, thus facilitating enzymatic acylation (at 9-C of compound 2) as an electrophile onto a PIQ scaffold (e.g., makaluvamine M). The sequence of events from an aldehyde to acyl-CoA is part of the fatty alcohol cycle pathway in intermediary metabolism.

1. Proposed Enzymatic Conversion of Compound 1 into Compound 1b via Dehydrogenase and Acylation with Compound 2 for the Biogenesis of Atkamine .

1

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a The aldehyde scaffold is illustrated in red.

On the other hand, we propose an alternative biogenesis of atkamine via an α-thiolated aldehyde intermediate for addition with an 18,20-Br makaluvamine M derivative (3). As illustrated in Scheme A, compound 1 is enzymatically transformed via the following steps: α-bromination via a haloperoxidase (e.g., HOBr) into (Z)-2-bromodocos-15-enal (1c); glutathione conjugation of the α-bromo via glutathione S-transferase (GST) into 2-(S-glutathionyl)-(Z)-docos-15-enal (1d); reduced glutathione (GSH) trimming to cysteine S-conjugate via γ-glutamyl transpeptidase into 2-(S-cysteinyl)-(Z)-docos-15-enal (1e); and thiol liberation to the α-thiolated aldehyde via pyridoxal-5′-phosphate (PLP)-dependent β-lyase into activated (Z)-2-(alkylthio)­docos-15-enal (1f). −

2. Postulated Enzymatic Conversion of (A) Compound 1 into Compound 1f and (B) Compound 3 into Atkamine .

2

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a The aldehyde scaffold is illustrated in red. An alternative pathway using 18,20-Br makaluvamine D (9) is presented in Scheme S2.

In Scheme B, the incorporation of α-thioaldehyde 1f to compound 3 may occur through an enol addition (at the 15-C position of compound 3) to a bromonium ion forms intermediate 4. Subsequent electrophilic aromatic substitution (EAS) to the activated carbon atom of the PIQ core (at the 9-C position of compound 4), the loss of HBr to form an imine, and etherification establishes the azepine ring system. Next, cyclization of the sulfur atom with dibromophenol (at the 21-C position of compound 7), followed by dehydrobromination (at the 20-C position of compound 8), provides atkamine. The in vivo incorporation of sulfur for PIQs is not established, so the exact pathway (e.g., thiol–disulfide exchange or Michael addition) and timing (e.g., before/after makaluvamine or discorhabdin scaffold) are speculative. ,,,

Conclusions

The structural elucidation of a putative atkamine lipid precursor, (Z)-docos-15-enal (1), the first aldehyde isolated from the Latrunculia genus of sponges, was achieved by using lipid-fragment-based experimental and computational approaches. DP4+/DFT structure-probability calculations and ab initio NMR CS computational data validated the (Z)-configuration of the double bond, whereas online OzESI-MS validated the placement of the double bond at the C-15/C-16 position by characteristic ozonolysis products using high-resolution mass spectrometry. Postulated enzymatic conversions of compound 1 to atkamine via acyl-CoA and α-thiolated derivatives were discussed.

The unique structure of atkamine, the only PIQ bearing a lipid side chain, warrants further investigation of its biosynthesis and potential biological properties, given the current lack of additional reported studies. Future mechanistic and synthetic studies incorporating compound 1 as an intermediate may generate atkamine analogs for biological assays and for pharmacokinetic and pharmacodynamic studies. A comparison of atkamine with PIQs and other lipid alkaloids, such as the pentacyclic ingenamine and mandagamine classes, which possess cis-alkenes in an aliphatic ring, may shed light on possible mechanisms of action and cellular targets, guiding the development of more targeted molecules that combine polycyclic alkaloids with lipid moieties. ,,−

Experimental Section

Sponge Collection

The Latrunculia sponges were collected from the FV Ocean Explorer and FV Alaska Provider during NOAA’s biannual groundfish bottom trawl survey in the Aleutian Islands. Sponges were collected between 10 June and 14 July 2024 in the North Pacific at Bering Sea at depths between 123 and 324 m (Table S4). Upon collection, sponges were stored in −20 °C chest freezers and shipped to Dr. Mark T. Hamann’s MUSC laboratory (Charleston, SC) at the conclusion of the summer surveys. These sponges were collected as bycatch during the survey and were authorized by the NOAA AFSC for research use.

Taxonomic Identification

L. oparinae (olive green) and L. hamanni (brown/purple) sponges were characterized by microsclere morphology as reported in “A guide to the deep-water sponges of the Aleutian Island Archipelago” by R. Stone et al., 2011, and “New taxa and arrangements within the family Latrunculiidae (Demospongiae, Poecilosclerida)” by Kelly et al., 2016. , Spicules were extracted using an aqueous bleach solution, and images (400× magnification) were captured via a microscope (LW Scientific, Lawrenceville, GA, USA). TLC of 1 mg/mL EtOH extracts for each species using an isocratic gradient (10% MeOH/90% DCM) revealed distinct metabolites (Figure S9).

Extraction and Purification

A total of 5.84 kg of lyophilized L. oparinae and L. hamanni sponges were extracted with organic solvents (5 L × 3): 1:4 DCM/Hex, and 100% EtOH. The crude EtOH extract (122 g) was subjected to flash silica gel chromatography to obtain the following fractions: 100% DCM, 5% methanol (MeOH)/DCM, 5% MeOH/DCM w/ca. 1% trifluoroacetic acid (TFA), 5% MeOH/DCM w/ca. 1% TFA, and 100% MeOH w/ca. 1% TFA. The 100% DCM fraction was subjected to additional flash silica chromatography using an isocratic gradient of 1:9 EtOAc/Hex. Fractions stained with dinitrophenylhydrazine (DNP) were combined and concentrated. Further purification was achieved via silica HPLC using a linear gradient from 0 to 15% DCM in hexanes over 30 min at a flow rate of 5.0 mL/min, yielding 4.5 mg of compound 1 as a transparent oil. The isolation scheme is illustrated in Scheme S1.

General Experimental Procedures

1H, 13C, and HMBC NMR spectra were recorded on a Bruker Avance II 600 MHz with UltraShield Plus magnet technology (Bruker BioSpin, Rheinstetten, Germany), and a probe temperature of 307 K. Samples were dissolved using deuterated chloroform (CDCl3) as a solvent. Chemical shifts are given in parts per million (ppm) (δ relative to the residual solvent peak for 1H and 13C).

Precoated TLC sheets of silica gel 60, Silicycle SIL G/UV254, and a dinitrophenylhydrazine (DNP) stain were used to visualize aldehyde-containing fractions. SiliaFlash irregular silica gel P60 (40–63 μm mesh, 60 Å) and Fisher chromatographic silica gel (200–425 μm mesh, 60 Å) were utilized for the primary and secondary silica flash chromatography steps, respectively. HPLC was conducted with a Waters 486 Tunable Absorbance Detector and Automated Gradient Controller (Waters Corp., Milford, MA, USA), and a Luna 10 u Silica 100 Å 250 mm × 21.2 mm column [Phenomenex, Torrance, CA, USA]. All compounds were determined to be ≥95% pure by HPLC and NMR analyses.

Spectroscopic Characterization of Natural (Z)-Docos-15-enal (1)

1H NMR (600 MHz, CDCl3) δH, (mult., J in Hz): δ: 9.78 (1H, t, 1.9), 5.36 (2H, m), 2.43 (2H, td, 1.9, 7.4), 2.02 (4H, m), 1.64 (2H, m), 1.28 (28H, m), and 0.90 (3H, t, 7.0). 13C NMR (600 MHz, CDCl3) δC (type): δ: 203.0 (C), 129.9 (overlapped, CH), 43.9 (CH2), 31.79, 29.78, 29.75, 29.65, 29.64, 29.58, 29.56, 29.43, 29.36, 29.32, 29.18, 29.18, 27.22, 27.21, 22.66, 22.10 (CH2), and 14.1 (CH3). ESI-MS: m/z 322.3464 [M + NH4–H2O]+; C22H42O (calculated for 322.3468 with Δppm = −1.24).

Online Ozonolysis LC-ESI-MS (OzESI) Determination of CC Position

All LC-MS analyses were carried out using a Vanquish Horizon UHPLC (Thermo Fisher Scientific) coupled to a Q Exactive HF mass spectrometer (Thermo Fisher Scientific). Mobile phases for LC separation consisted of ACN/H2O (1:1, v/v) and IPA/ACN/H2O (88:10:2. v/v/v), respectively, both containing 5 mM ammonium formate and 0.1% formic acid. Other details of LC separation have been published previously. Online ozonolysis setup as well as mass spectrometer parameters were applied as detailed previously, , with 5% ozone teeing to the sheath gas line of the ionization source. MS1 mass resolution was set at 120,000.

Computational Analyses

Possible relative configurations of the aldehyde alkene (olefin region) were assessed using in silico ChemDraw (Revvity Signals Software, Waltham, Massachusetts, 2024, version 23.11) 1H and 13C CS predictions, along with DP4+ structure-probability analyses by comparing experimental and calculated NMR data. The 2D structures of the cis (Z) and trans (E) configurations were sketched in Maestro (Maestro, Schrödinger, LLC, New York, NY, USA) and 3D-energy was minimized at physiological pH 7.4 using the LigPrep (Schrödinger software Release 2020–4 LigPrep, Schrödinger, LLC, New York, NY, USA) module of the Schrödinger software. An exhaustive conformational search was performed on both configurations of the molecule using a combination of several commercial and academic conformational search tools: Omega Macrocycle and Omega Classic (OpenEye Scientific, Santa Fe, New Mexico, USA); ConfGenX, MacroModel, and Prime-MCS (Schrodinger, New York, New York, USA); ForceGen (Optibrium, Waterbeach, England); MOE (Chemical Computing Group, Montreal, Quebec, Canada).

The energy window cutoff was set to 10 kcal/mol to cover all possible lowest-energy conformers. Redundant conformers were eliminated using an RMSD cutoff of 0.5 Å. The conformations that showed >1% Boltzmann population from molecular mechanics calculations were further geometry-optimized using DFT with mPW1PW91/6–311 + G­(d,p), using Gaussian 16 Rev. B.01 software (Gaussian, Inc., Wallingford, CT, USA). CHCl3 was used as a solvent with the IEFPCM solvation model. All of the geometry optimizations included subsequent frequency calculations to verify that true minima on the potential energy surface were obtained. The Boltzmann-weighted optimized low-energy conformers were used in the chemical shift calculations using GIAO NMR at the DFT PCM-mPW1PW91/6–311 + G­(d,p)//B3LYP/6–31 + G­(d) and PCM-B3LYP/6–311 + G­(d,p)//B3LYP/6–31 + G­(d) levels of theory.

Supplementary Material

ao5c11024_si_001.pdf (8.4MB, pdf)

Acknowledgments

The authors thank the NOAA AFSC Leg 1 and 2 scientists (Bethany Riggle, Alexandra Dowlin, Sean Rooney, Sarah Friedman, Pearl Rojas, Nate Raring, Laura Beckmann, Susanne McDermott, Margaret Siple, Alex Guffey, and Rick Hipbshman) and FV Ocean Explorer (OEX; Vessel 148; Cruise 202401) crew members: captain (Dan); first mate (Raf); chief engineer (Chip); cook (Larry Carroll); and deckhands (Shaun Weaver and Tanner Gaiser) for their support during the 2024 Aleutian Islands Groundfish Bottom Trawl Survey. Additional information about the survey is available here: https://www.fisheries.noaa.gov/alaska/ecosystems/alaska-fish-research-surveys#aleutian-islands-bottom-trawl-survey. The authors thank the College of Charleston and instrument manager, Stephanie Boussert, for infrastructure support.

Glossary

Abbreviations

PIQ

pyrroloiminoquinone

NOAA

National Oceanic and Atmospheric Administration

AFSC

Alaska Fisheries Science Center

FV

fishing vessel

OEX

Ocean Explorer

AKP

Alaska Provider

DP4

diastereomer prediction 4

DFT

density functional theory

OzESI

LC-ESI-MS ozonolysis

TFA

trifluoroacetic acid

DNP

dinitrophenylhydrazine

GST

gluthathione S-transferase

ALDH

aldehyde dehydrogenase

CoA

coenzyme A

GSH

reduced gluthathione

PLP

pyridoxal-5′-phosphate

The data underlying this study are available in the published article and its Supporting Information. All raw NMR data have been deposited in the Natural Products Magnetic Resonance Database (NP-MRD) under accession number NP0351623.

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsomega.5c11024.

  • Isolation scheme, spectroscopic, computational, and taxonomic details (Figures S1–S9) (Tables S1–S4) (Schemes S1 and S2) (PDF)

M.M.B. conceived the study, designed and performed the experiments, analyzed the data, and wrote the manuscript. C.F.D. provided the nonpolar subfractions and assisted with postulating biosyntheses. J.S.W. and R.T.W. performed DP4+/DFT structure-probability calculations, provided technical support, and experimental infrastructure. R.P.S., G.R.H., and G.S.H. assisted with sponge collection logistics and taxonomy. A.S.A. helped postulate biosyntheses. A.R.S. contributed to the chromatography purification of the molecule. F.A.M. and Q.Z. contributed to the determination of the CC position. C.F.D. and M.T.H. contributed to project supervision and advised on experimental design and data interpretation. All authors have approved the final version of the manuscript.

This research was funded by NIGMS R01GM145845 (M.T.H.) and partially by NIDDK R01DK123499 (Q.Z.).

The authors declare no competing financial interest.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

ao5c11024_si_001.pdf (8.4MB, pdf)

Data Availability Statement

The data underlying this study are available in the published article and its Supporting Information. All raw NMR data have been deposited in the Natural Products Magnetic Resonance Database (NP-MRD) under accession number NP0351623.

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