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Prymnesin-2

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Prymnesin-2
Structure of prymnesin-2
Names
IUPAC name
(11S)-1-[(2R,3R,4R,5S,6R)-6-[(2R,3S,4R,4aR,6R,8aR)-6-[(2R,3S,4aR,6S,8R,8aS)-6-[(2R,3R,4aR,6S,8R, 8aR)-6-[(2S,3S,4aS,6R,8aR)-2-[(1S,3R,5S,7S,10S,12R,14S,16S,21R,22R)-7-[(1Z,3Z,6R,8Z,10Z,18Z)-6-amino-19-chlorononadeca-1,3,8,10,18-pentaen-12,16-diynyl]-22-hydroxy-2,6,11,15,20-pentaoxapentacyclo[12.9.0.03,12.05,10.016,21]tricosan-19-yl]-3-methyl-2,3,4,4a,6,7,8,8a-octahydropyrano[3,2-b]pyran-2-yl]-8-chloro-3-hydroxy-2,3,4,4a,6,7,8,8a-octahydropyrano[3,2-b]pyran-2-yl]-11-chloro-3-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxyhexadeca-13,15-diyne-2,4,6,7,8,9,10-heptol
Other names
PRM2[1]
Identifiers
3D model (JSmol)
  • InChI=1S/C96H136Cl3NO35/c1-3-4-15-23-47(98)75(109)79(113)80(114)76(110)49(102)35-50(103)88(135-96-85(119)78(112)74(43-101)132-96)51(104)38-70-77(111)81(115)82(116)94(131-70)95-84(118)83(117)93-62(130-95)31-30-61(129-93)90-54(107)39-72-87(133-90)48(99)34-71(126-72)91-55(108)40-73-92(134-91)53(106)36-64(125-73)57-26-27-58-63(121-57)33-44(2)86(127-58)59-28-29-60-89(128-59)52(105)37-65-67(123-60)42-68-69(124-65)41-66-56(122-68)25-24-46(120-66)22-18-14-17-21-45(100)20-16-12-10-8-6-5-7-9-11-13-19-32-97/h1,8,10,12,14,16-19,22,32,44-96,101-119H,7,9,20-21,23-31,33-43,100H2,2H3/b10-8+,16-12+,17-14+,22-18+,32-19+/t44-,45+,46+,47-,48+,49?,50?,51?,52+,53+,54-,55+,56-,57+,58+,59?,60-,61?,62+,63-,64?,65-,66-,67-,68+,69+,70+,71?,72+,73+,74+,75?,76?,77-,78+,79?,80?,81+,82-,83+,84-,85+,86-,87+,88?,89+,90+,91+,92+,93-,94?,95+,96+/m0/s1
    Key: WCHCDYFGLWOFCV-GUPVPWLLSA-N
  • C[C@H]1C[C@]2([H])O[C@@H](C3C[C@H]([C@@]4([H])O[C@@H](C5C[C@H]([C@@]6([H])O[C@@H](C7CC[C@@]8([H])O[C@@H](C9O[C@@H]([C@@H]([C@H]([C@@H]9O)O)O)CC(C(C(CC(C(C(C(C([C@H](CC#CC#C)Cl)O)O)O)O)O)O)O[C@H]%10O[C@@H]([C@H]([C@H]%10O)O)CO)O)[C@H]([C@H]([C@@]8([H])O7)O)O)[C@H](C[C@@]6([H])O5)O)Cl)[C@@H](C[C@@]4([H])O3)O)O)CC[C@@]2([H])O[C@@H]1C%11CC[C@]%12([H])O[C@@]%13([H])C[C@@]%14([H])O[C@@]%15([H])CC[C@@H](/C=C/C=C/C[C@@H](C/C=C/C=C/C#CCCC#C/C=C/Cl)N)O[C@@]%15([H])C[C@@]%14([H])O[C@@]%13([H])C[C@H]([C@@]%12([H])O%11)O
Properties
C96H136Cl3NO35
Molar mass 1970.47 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Prymnesin-2 is an organic compound that is secreted by the haptophyte Prymnesium parvum. It belongs to the prymnesin family and has potent hemolytic and ichthyotoxic properties. In a purified form it appears as a pale yellow solid.[2] P. parvum is responsible for red harmful algal blooms worldwide, causing massive fish killings. When these algal blooms occur, this compound poses a threat to the local fishing industry. This is especially true for brackish water, as the compound can reach critical concentrations more easily.[2]

Structure and reactivity

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The structural formula of prymnesin-2 is: C96H136Cl3NO35. The compound exhibits multiple chiral centers. The molecule is amphoteric, which means that it can act both as base and an acid. This is because all 16 hydroxyls, except for one at C32, are concentrated on carbons C48-84, and there α-L-xylofuranose moiety at C77.[1] This might lead to interaction with biomembranes, which is thought to be the basis of its toxicity.[2] The difference between prymnesin-1 and prymnesin-2 is the glycosidic residues: L-arabinose, D-galactose and D-ribose, yet prymnesin-2 and prymnesin-1 show comparable activities. Prymnesins also have unique features: The possession of only one methyl, but three chlorine atoms, four C-C triple bonds, sugars and an amino group.[3]

Biosynthesis

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Prymnesin-1 and prymnesin-2 are both are derived from acetate-related (i.e. polyketide) metabolism, based on knowledge about the structure of the prymnesins. In general primary and secondary metabolites such as fatty acids, polyketides and non-ribosomal peptides are synthesised by the acetate pathway.[4] In 2024 the backbone of A-type prymnesins like prymnesin-2 was reported to be made by giant polyketide synthase enzymes dubbed the "PKZILLAs".[5]

Mechanism of action

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The mechanism of action of prymnesin-2 remains to be determined.[3] Prymnesin-2 and prymnesin-1 show comparable activities. Prymnesin-2 has shown multiple functionalities, such as potent hemolytic activity and diverse biological activities, such as mouse lethality, ichthyotoxicity and activity inducing Ca+2 influx into cultured cells. The hemolytic potency of prymnesin-2 exceeds that of plant saponin by 50.000 times.[6]

Prymnesin-2 causes hemolysis by direct interaction between toxin and cell surface. Partly due to interaction with cellular lipids, mainly to interaction with a specific binding site on the blood cell surface. This is supported by the observation of competitive inhibition by the prymnesin-2 analogues, which assume the presence of a specific binding site on the blood cell surface. Also the process of toxin molecule aggregation may be involved in the main mechanism of the haemolytic activity.[6]

Toxicity

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Prymnesin-2 is an ichthyotoxic compound with the ability to hemolyze blood. 2.5 nM is needed for a 50% hemolysis rate of a 1% rat blood cell suspension, and 9 nM is enough for killing freshwater fish. The hemolytic and ichthyotoxic properties increase when the pH of the solution rises from 7 to 8.[7] Prymnesin-2 causes calcium ion influx into C6 rat glioma cells at a concentration of 70 nM.[8]

Besides the lytic effect on blood cells, hepatocytes, Hela cells and artificial liposomes are affected by prymnesin-2.

As seen in the table below, prymnesin-2 is highly hemolytic for blood cells of different animal species, even when compared to the already highly hemolytic toxin saponin.

Table1. Sensitivities of blood cells from different animal species
Prymnesin-2 (nM) Saponin (nM) Relative to saponin
Mouse 2.5 17000 6800
Rabbit 1.7 15000 8800
Dog 0.5 25000 50000
Sheep 0.6 23000 38000
Chicken 1.9 17000 8900
Carp 1.6 11500 7200

Effects on animals

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In the US, the first recorded P. parvum bloom occurred in 1985 in a semi-arid region of the country (Pecos River, Texas).[9] Since then, the incidence of P. parvum blooms dramatically increased in the US, where the organism has invaded lakes and rivers throughout southern regions and most recently into northern regions. The magnitude of P. parvum blooms are also increasing over the past decade compared to 30 years ago, with massive fish killings as result.[10][11][12]

See also

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Scholia has a profile for prymnesin-2 (Q55630719).

References

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  1. ^ a b Igarashi, Tomoji; Satake, Masayuki; Yasumoto, Takeshi (1999). "Structures and Partial Stereochemical Assignments for Prymnesin-1 and Prymnesin-2: Potent Hemolytic and Ichthyotoxic Glycosides Isolated from the Red Tide AlgaPrymnesium parvum". Journal of the American Chemical Society. 121 (37). American Chemical Society (ACS): 8499–8511. doi:10.1021/ja991740e. ISSN 0002-7863.
  2. ^ a b c Igarashi, Tomoji; Satake, Masayuki; Yasumoto, Takeshi (1996). "Prymnesin-2: A Potent Ichthyotoxic and Hemolytic Glycoside Isolated from the Red Tide Alga Prymnesium parvum". Journal of the American Chemical Society. 118 (2): 479–480. doi:10.1021/ja9534112.
  3. ^ a b Yasumoto, Takeshi (2001). "The chemistry and biological function of natural marine toxins". The Chemical Record. 1 (3): 228–242. doi:10.1002/tcr.1010. ISSN 1528-0691. PMID 11895121.
  4. ^ Manning, Schonna R.; La Claire, John W. (2010-03-16). "Prymnesins: Toxic Metabolites of the Golden Alga, Prymnesium parvum Carter (Haptophyta)". Marine Drugs. 8 (3): 678–704. doi:10.3390/md8030678. PMC 2857367. PMID 20411121.
  5. ^ Fallon, Timothy R.; Shende, Vikram V.; Wierzbicki, Igor H.; Pendleton, Amanda L.; Watervoort, Nathan F.; Auber, Robert P.; Gonzalez, David J.; Wisecaver, Jennifer H.; Moore, Bradley S. (2024-08-09). "Giant polyketide synthase enzymes in the biosynthesis of giant marine polyether toxins". Science. 385 (6709): 671–678. doi:10.1126/science.ado3290. ISSN 0036-8075.
  6. ^ a b Igarashi, T.; Aritake, S.; Yasumoto, T. (1998). "Biological activities of prymnesin-2 isolated from a red tide alga Prymnesium parvum". Natural Toxins. 6 (1): 35–41. doi:10.1002/(SICI)1522-7189(199802)6:1<35::AID-NT7>3.0.CO;2-7. ISSN 1056-9014. PMID 9851510.
  7. ^ Granéli, Edna; Salomon, Paulo S. (1 February 2010). "Factors Influencing Allelopathy and Toxicity in Prymnesium parvum". JAWRA Journal of the American Water Resources Association. 46 (1): 108–120. Bibcode:2010JAWRA..46..108G. doi:10.1111/j.1752-1688.2009.00395.x. ISSN 1752-1688.
  8. ^ Morohashi, Akio; Satake, Masayuki; Oshima, Yasukatsu; Igarashi, Tomoji; Yasumoto, Takeshi (2001). "Absolute configuration at C14 and C85 in prymnesin-2, a potent hemolytic and ichthyotoxic glycoside isolated from the red tide alga Prymnesium parvum". Chirality. 13 (9): 601–605. doi:10.1002/chir.1184. ISSN 1520-636X. PMID 11579456.
  9. ^ James T. L., De La Cruz A.. Prymnesium parvum Carter (Chrysophyceae) as a suspect of mass mortalities of fish and shellfish communities in western Texas, Texas Journal of Science, 1989, vol. 41 (pp. 429-430).
  10. ^ Roelke, Daniel; Augustine, Sarah; Buyukates, Yesim (2003-11-01). "Fundamental Predictability in Multispecies Competition: The Influence of Large Disturbance". The American Naturalist. 162 (5): 615–623. doi:10.1086/378750. ISSN 0003-0147. PMID 14618539. S2CID 19980618.
  11. ^ Buyukates, Yesim; Roelke, Daniel (2005-10-01). "Influence of Pulsed Inflows and Nutrient Loading on Zooplankton and Phytoplankton Community Structure and Biomass in Microcosm Experiments Using Estuarine Assemblages". Hydrobiologia. 548 (1): 233–249. doi:10.1007/s10750-005-5195-x. ISSN 0018-8158. S2CID 40194710.
  12. ^ Miller, Carrie J.; Roelke, Daniel L.; Davis, Stephen E.; Li, Hsiu-Ping; Gable, George (2008). "The role of inflow magnitude and frequency on plankton communities from the Guadalupe Estuary, Texas, USA: Findings from microcosm experiments". Estuarine, Coastal and Shelf Science. 80 (1): 67–73. Bibcode:2008ECSS...80...67M. doi:10.1016/j.ecss.2008.07.006.
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