Microcystins—or cyanoginosins—are a class of

cyanotoxin Cyanotoxins are toxins produced by cyanobacteria (also known as blue-green algae). Cyanobacteria are found almost everywhere, but particularly in lakes and in the ocean where, under high concentration of phosphorus conditions, they reproduce exp ...

s, which are

toxin A toxin is a naturally occurring poison produced by metabolic activities of living cells or organisms. They occur especially as proteins, often conjugated. The term was first used by organic chemist Ludwig Brieger (1849–1919), derived ...

s produced by

cyanobacteria Cyanobacteria ( ) are a group of autotrophic gram-negative bacteria that can obtain biological energy via oxygenic photosynthesis. The name "cyanobacteria" () refers to their bluish green (cyan) color, which forms the basis of cyanobacteri ...

, sometimes known as blue-green algae. Over 250 different microcystins have been discovered so far, of which microcystin-LR is the most common. Chemically they are cyclic heptapeptides produced through

nonribosomal peptide Nonribosomal peptides (NRP) are a class of peptide secondary metabolites, usually produced by microorganisms like bacterium, bacteria and fungi. Nonribosomal peptides are also found in higher organisms, such as nudibranchs, but are thought to be ma ...

synthases. Cyanobacteria can produce microcystins in large quantities during

algal bloom An algal bloom or algae bloom is a rapid increase or accumulation in the population of algae in fresh water or marine water systems. It is often recognized by the discoloration in the water from the algae's pigments. The term ''algae'' encompass ...

s which then pose a major threat to drinking and irrigation water supplies, and the environment at large.

Characteristics

Microcystins—or cyanoginosins—are a class of toxins produced by certain freshwater

; primarily ''

Microcystis aeruginosa ''Microcystis aeruginosa'' is a species of freshwater cyanobacteria that can form harmful algal blooms of economic and ecological importance. They are the most common toxic cyanobacterial bloom in eutrophic fresh water. Cyanobacteria produce neu ...

'' but also other '' Microcystis'', as well as members of the ''

Planktothrix ''Planktothrix'' is a diverse genus of filamentous cyanobacteria observed to amass in algal blooms in water ecosystems across the globe. Like all Oscillatoriales, ''Planktothrix'' species have no heterocyst, heterocysts and no akinetes. ''Plankto ...

'', ''

Anabaena ''Anabaena'' is a genus of filamentous cyanobacteria that exist as plankton. They are known for nitrogen-fixing abilities, and they form symbiotic relationships with certain plants, such as the mosquito fern. They are one of four genera of cyan ...

'', ''

Oscillatoria ''Oscillatoria'' is a genus of filamentous cyanobacteria. It is often found in freshwater environments. Its name refers to the oscillating motion of its filaments as they slide against each other to position the colony to face a light source. ...

'' and ''

Nostoc ''Nostoc'', also known as star jelly, troll's butter, spit of moon, fallen star, witch's butter (not to be confused with the fungi commonly known as witches' butter), and witch's jelly, is the most common genus of cyanobacteria found in a variety ...

'' genera. Microcystin-LR (i.e. ''X'' = leucine, ''Z'' = arginine) is the most toxic form of over 80 known toxic variants, and is also the most studied by chemists, pharmacologists, biologists, and ecologists. Microcystin-containing 'blooms' are a problem worldwide, including China, Brazil, Australia, South Africa, the United States and much of Europe.

Hartebeespoort Dam Hartbeespoort Dam (also known as ''Harties'') is an arch type dam situated in the North West (South African province), North West Province of South Africa. It lies in a valley to the south of the Magaliesberg mountain range and north of the Witwa ...

in South Africa is one of the most contaminated sites in Africa, and possibly in the world.

Chemistry

Microcystins have a common structural framework of D-Ala¹-''X''²-³-''Z''⁴-Adda⁵-D-γ-Glu⁶-⁷, where ''X'' and ''Z'' are variable amino acids; the systematic name "microcystin-''XZ''" (MC-''XZ'' in short) is then assigned based on the one letter codes (if available; longer codes otherwise) of the amino acids. If the molecule show any other modification, the differences are noted in square brackets before "MC". Of these, several are uncommon non-

proteinogenic Proteinogenic amino acids are amino acids that are incorporated biosynthetically into proteins during translation from RNA. The word "proteinogenic" means "protein creating". Throughout known life, there are 22 genetically encoded (proteinogenic) ...

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

s: * D-Masp is D-erythro-β-methyl-isoaspartic acid, a derivative of

aspartic acid Aspartic acid (symbol Asp or D; the ionic form is known as aspartate), is an α-amino acid that is used in the biosynthesis of proteins. The L-isomer of aspartic acid is one of the 22 proteinogenic amino acids, i.e., the building blocks of protei ...

in β-amino acid form; * Adda is (all-''S'',all-''E'')-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4,6-dienoic acid, a β-amino acid exclusively found in microcystin and the related nodularin; * Mdha is N-methyldehydroalanine, a derivative of

dehydroalanine Dehydroalanine (Cα,β-didehydroalanine, α,β-di-dehydroalanine, 2-aminoacrylate, or 2,3-didehydroalanine) is a dehydroamino acid. It does not exist in its free form, but it occurs naturally as a residue found in peptides of microbial origin. As ...

. In nodularin it is replaced by Mdhb (N-methyldehydrobutyrine), another

dehydroamino acid In biochemistry, a dehydroamino acid or α,β-dehydroamino acid is an amino acids, usually with a C=C double bond in its side chain. Dehydroamino acids are not coded by DNA, but arise via post-translational modification. Examples A common dehydro ...

derivative.

Mechanism of action

Microcystins covalently bond to and inhibit protein phosphatases PP1 and

PP2A Protein phosphatase 2 (PP2), also known as PP2A, is an enzyme that in humans is encoded by the ''PPP2CA'' gene. The PP2A heterotrimeric protein phosphatase is ubiquitously expressed, accounting for a large fraction of phosphatase activity in ...

and can thus cause pansteatitis. The ADDA residue is key to this functionality: greatly simplified synthetic analogues consisting of ADDA and one additional amino acid can show the same inhibiting function.

Factors affecting production

The microcystin-producing '' Microcystis'' is a genus of freshwater cyanobacteria and thrives in warm water conditions, especially in stagnant waters. The EPA predicted in 2013 that climate change and changing environmental conditions may lead to harmful algae growth and may negatively impact human health. Algal growth is also encouraged through the process of

eutrophication Eutrophication is a general term describing a process in which nutrients accumulate in a body of water, resulting in an increased growth of organisms that may deplete the oxygen in the water; ie. the process of too many plants growing on the s ...

(oversupply of nutrients). In particular, dissolved reactive phosphorus promotes algal growth. Microcystins may have evolved as a way to deal with low iron supply in cyanobacteria: the molecule binds iron, and non-producing strains are significantly worse at coping with low iron levels. Low iron supply up-regulates ''McyD'', one of the microcystin synthetic operons. Sufficient iron supply, however, can still boost microcystin production by making the bacterium better at photosynthesis, therefore producing sufficient ATP for MC biosynthesis. Microcystin production is also positively correlated with temperature. Bright light and red light increases transcription of ''McyD'', but blue light reduces it. A wide range of other factors such as pH may also affect MC production, but comparison is complicated due to a lack of standard testing conditions.

Exposure pathways

There are several ways of exposure to these hepatotoxins that humans can encounter one of which is through recreational activities like swimming, surfing, fishing, and other activities involving direct contact with contaminated water.Funari E, Testai E. 2008. Human health risk assessment related to cyanotoxins exposure. Critical Reviews in Toxicology. 38(2). 97–125 Another rare, yet extremely toxic, route of exposure that has been identified by scientists is through hemodialysis surgeries. One of the fatal cases for microcystic intoxication through hemodialysis was studied in Brazil where 48% of patients that received the surgery in a specific period of time died because the water used in the procedure was found to be contaminated.Azevedo, Sandra M.F.O, Wayne W Carmichael, Elise M Jochimsen, Kenneth L Rinehart, Sharon Lau, Glen R Shaw, and Geoff K Eaglesham. 2002. “Human Intoxication by Microcystins During Renal Dialysis Treatment in Caruaru—Brazil.” Toxicology (Amsterdam) 181. 441–446. Microcystins are chemically stable over a wide range of temperature and pH, possibly as a result of their cyclic structure. Microcystin-LR water contamination is resistant to boiling and microwave treatments. Microcystin-producing bacteria

s can overwhelm the filter capacities of

water treatment Water treatment is any process that improves the quality of water to make it appropriate for a specific end-use. The end use may be drinking, industrial water supply, irrigation, river flow maintenance, water recreation or many other uses, ...

plants. Some evidence shows the toxin can be transported by

irrigation Irrigation (also referred to as watering of plants) is the practice of applying controlled amounts of water to land to help grow crops, landscape plants, and lawns. Irrigation has been a key aspect of agriculture for over 5,000 years and has bee ...

into the food chain.

Lake Erie blooms

In 2011, a record outbreak of blooming microcystis occurred in

Lake Erie Lake Erie ( ) is the fourth-largest lake by surface area of the five Great Lakes in North America and the eleventh-largest globally. It is the southernmost, shallowest, and smallest by volume of the Great Lakes and also has the shortest avera ...

, in part related to the wettest spring on record, and expanded lake bottom dead zones, reduced fish populations, fouled beaches, and damaged the local tourism industry, which generates more than $10 billion in revenue annually. In August 2014, the City of

Toledo, Ohio Toledo ( ) is a city in Lucas County, Ohio, United States, and its county seat. It is located at the western end of Lake Erie along the Maumee River. Toledo is the List of cities in Ohio, fourth-most populous city in Ohio and List of United Sta ...

detected unsafe levels of microcystin in its water supply due to harmful algal blooms in Lake Erie, the shallowest of the

Great Lakes The Great Lakes, also called the Great Lakes of North America, are a series of large interconnected freshwater lakes spanning the Canada–United States border. The five lakes are Lake Superior, Superior, Lake Michigan, Michigan, Lake Huron, H ...

. The city issued an advisory to approximately 500,000 people that the water was not safe for drinking or cooking. An Ohio state task force found that Lake Erie received more phosphorus than any other Great Lake, both from crop land, due to the farming practices, and from urban water-treatment centres.

San Francisco Bay Area

In 2016, microcystin had been found in San Francisco Bay Area shellfish in seawater, apparently from freshwater runoff, exacerbated by

drought A drought is a period of drier-than-normal conditions.Douville, H., K. Raghavan, J. Renwick, R.P. Allan, P.A. Arias, M. Barlow, R. Cerezo-Mota, A. Cherchi, T.Y. Gan, J. Gergis, D. Jiang, A. Khan, W. Pokam Mba, D. Rosenfeld, J. Tierney, ...

Iowa

In 2018, the Iowa Department of Natural Resources found microcystins at levels of 0.3 µg/L, or micrograms per liter ( ppb), in the raw water supplies of 15 out of 26 public water systems tested.Kate Payn
Toxic Bacteria Blooms Impacting Water Systems Across Iowa, DNR Survey Shows.
November 1, 2018. National Public Radio

Oregon

In 2023, the Oregon Department of Environmental Quality (DEQ) and Oregon Health Authority issued a cyanobacteria advisory for much of the

Willamette River The Willamette River ( ) is a major tributary of the Columbia River, accounting for 12 to 15 percent of the Columbia's flow. The Willamette's main stem is long, lying entirely in northwestern Oregon in the United States. Flowing northward ...

as it runs through Portland. The advisory affected the Willamette from the

Ross Island Ross Island is an island in Antarctica lying on the east side of McMurdo Sound and extending from Cape Bird in the north to Cape Armitage in the south, and a similar distance from Cape Royds in the west to Cape Crozier in the east. The isl ...

Lagoon through Cathedral Park. Testing by the DEQ showed microcystin levels at 549 ppb.

Human health effects upon exposure

Microcystins cannot be broken down by standard

proteases A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the formation of new protein products. They do ...

pepsin Pepsin is an endopeptidase that breaks down proteins into smaller peptides and amino acids. It is one of the main digestive enzymes in the digestive systems of humans and many other animals, where it helps digest the proteins in food. Pe ...

trypsin Trypsin is an enzyme in the first section of the small intestine that starts the digestion of protein molecules by cutting long chains of amino acids into smaller pieces. It is a serine protease from the PA clan superfamily, found in the dig ...

, collagenase, and chymotrypsin due to their cyclic chemical nature. They are hepatotoxic, i.e., able to cause serious damage to the

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

. Once ingested, microcystin travels to the liver via the bile acid transport system, where most is stored, though some remains in the blood stream and may contaminate tissue. Acute health effects of Microcystin-LR are abdominal pain, vomiting and nausea, diarrhea, headache, blistering around the mouth, and after inhalation sore throat, dry cough, and pneumonia. Studies suggest that the absorption of microcystins occurs in the gastrointestinal tract. Furthermore, it was found that these hepatotoxins inhibit the activity of protein enzymes phosphatase PP1 and PP2A causing hemorrhagic shock and were found to kill within 45 minutes in mice studies. There appears to be inadequate information to assess the carcinogenic potential of microcystins by applying EPA Guidelines for Carcinogen Risk Assessment. A few studies suggest a relationship may exist between liver and colorectral cancers and the occurrence of cyanobacteria in drinking water in China. Evidence is, however, limited due to limited ability to accurately assess and measure exposure.

Regulation

In the US, the EPA issued a health advisory in 2015.Drinking Water Health Advisory for the Cyanobacterial Microcystin Toxins
U.S. Environmental Protection Agency Office of Water, EPA Document Number: 820R15100, 75pp, 15 June 2015 A ten day Health Advisory was calculated for different ages which is considered protective of non-carcinogenic adverse health effects over a ten-day exposure to microcystins in drinking water: 0.3 μg/L for bottle-fed infants and young children of pre-school age and 1.6 μg/L for children of school age through adults.

References

External links

Harmful Algal Blooms (EPA)
n.d. retrieved 12 Nov 2018
Blue-Green Algae (Cyanobacteria) and their Toxins (Health Canada)Toxic cyanobacteria in water: A guide to their public health consequences, monitoring, and management (WHO)Cyanobacteria and Cyanotoxins: Information for Drinking Water Systems (EPA)
By Carl Zimmer, Aug. 7, 2014(The New York Times) {{Authority control Cyanotoxins Water quality indicators Cyanobacteria Hepatotoxins Algae Environmental chemistry Bacteriology Cyclic peptides