220 Marine Macro- and Microalgae: An Overview
the amount of such toxins—associated with a given phytoplankton bloom, are comparably less well
understood (Hackett et al. 2004). The ecological reason why dinoflagellates produce potent biotoxins is
not clear. Maybe such secondary metabolites act as allellochemical agents against other species competing
for a specific niche, as defense against predation, as enzyme regulation, or as sexual response induction
(feromones) (Cembella 2003; Sheng et al. 2010).
Toxin biosynthesis is apparently related to cell cycle and light-dependent events, but can also be
affected by other factors (i.e., nutrient availability, temperature, salinity). In the benthic dinoflagellate
Prorocentrum lima, dinophysistoxin-4 toxin synthesis is initiated in the G1 phase of the cell cycle but
persists into the S phase. On the other hand, the biosynthesis of spirolide toxin produced by Alexandrium
ostenfeldii is governed by such light-dependent mechanisms—since toxin concentration per cell quota
increases in the beginning of the dark period (probably corresponding to the G1 or S phase cell cycle)
(John et al. 2001). The biosynthesis of saxitoxin by Alexandrium fundyense occurs for 8–10 h during the
G1 phase, and its levels remain almost undetectable during the other phases of the cell cycle (TaroncherOldenburg et al. 1997).
Under nutrient-balanced conditions, toxin production is normally low—while increased production
is associated with recovery from various types of nutrient stress. Therefore, biosynthesis of both alkaloids
(e.g., saxitoxin) and polyketides (e.g., brevetoxins) appear to be related to nitrogen and carbon metabolism
deficiency. The synthesis of PSP toxins in Alexandrium fundyense was observed to increase when the
medium is enriched in nitrogen and reduced in phosphorous. The opposite, that is, very low content of
PSP toxins, was observed when the medium was rich in phosphate and poor in nitrogen (John and Flynn
2000). Several studies support the idea that nitrogen-limiting conditions increase PSP toxin levels (Wang
et al. 2002; Frangópulos et al. 2004; Han et al. 2016). This seems to be related to the increased availability
of intracellular arginine (an important precursor for biosynthesis of PSP toxins), due to a reduced demand
of competing phosphorous-dependent pathways involved in cell division. High N:P ratios apparently
influence higher toxin production of ciguatoxin in Gamberdiscus (Chinain et al. 2010) and brevetoxin by
Karenia brevis—which is also influenced by limited-phosphorous concentration (Hardison et al. 2013).
However, the influence of enhanced phosphate supply upon toxin content is still a matter of debate. In
axenic Alexandrium tamarense-cultured in low-level phosphate conditions and supplemented with nitrate
and phosphate, toxin production was obtained when compared to the outcome under high nutrient levels
(Hu et al. 2006).
Induction or cellular accumulation of algal toxins during unbalanced growth/cell stress has become
a paradigm in attempts to understand modulation of phytoplankton toxicity by environmental factors.
Nonetheless, different patterns may extensively vary between species (Kibler et al. 2012)—and even
among strains with similar geographic distribution (Etheridge and Roesler 2005). The high degree of
variability in toxicity observed for a number of HAB species reflects the complex relationship between
environmental and genetic factors (Adolf et al. 2009; Hardison et al. 2013). Changes in total cellular
toxicity of a dinoflagellate cell, in response to environmental factors, depends upon both the absolute
toxin concentration (or the rate of production of toxin) and the relative toxin composition (Etheridge and
Roesler 2005). Some cells may exhibit higher toxicity (even when they have lower toxin concentration)
than others, depending on the established toxin profile. Alexandrium fundyense was found to have higher
toxicity (at 5ºC) owing to its toxin profile containing a higher fraction of saxitoxins and gonyatoxins, but
a lower total cell concentration at 20ºC (Etheridge and Roesler 2005).
Cellular toxicity among different isolates in laboratory cultures may be substantially lower when
compared to fresh bloom samples. Karlodinium veneficum cultivated in laboratory exhibited lower
content of karlotoxin (10 times less) than their counterparts from bloom samples; possibly culturing
conditions favor low toxin genotypes, or conditions in situ lead to enhanced toxicity (Adolf et al. 2009).
In addition, increased cellular toxicity in dinoflagellates may relate to the presence of bacteria in the
media, or via establishment of an endosymbiotic relationship (Steidinger and Baden 1984). Bacteria have
been associated with HABs events in the case of both planktonic and benthic dinoflagellates (Schweikert
and Meyer 2001); hence, truly axenic cultures of dinoflagellates are extremely difficult to obtain. The
bottom line is that bacteria may contribute to variation of toxin production, either inside the cell or secreted
to the culture medium. Some studies referred to de novo synthesis of some toxins, as shown in axenic
the amount of such toxins—associated with a given phytoplankton bloom, are comparably less well
understood (Hackett et al. 2004). The ecological reason why dinoflagellates produce potent biotoxins is
not clear. Maybe such secondary metabolites act as allellochemical agents against other species competing
for a specific niche, as defense against predation, as enzyme regulation, or as sexual response induction
(feromones) (Cembella 2003; Sheng et al. 2010).
Toxin biosynthesis is apparently related to cell cycle and light-dependent events, but can also be
affected by other factors (i.e., nutrient availability, temperature, salinity). In the benthic dinoflagellate
Prorocentrum lima, dinophysistoxin-4 toxin synthesis is initiated in the G1 phase of the cell cycle but
persists into the S phase. On the other hand, the biosynthesis of spirolide toxin produced by Alexandrium
ostenfeldii is governed by such light-dependent mechanisms—since toxin concentration per cell quota
increases in the beginning of the dark period (probably corresponding to the G1 or S phase cell cycle)
(John et al. 2001). The biosynthesis of saxitoxin by Alexandrium fundyense occurs for 8–10 h during the
G1 phase, and its levels remain almost undetectable during the other phases of the cell cycle (TaroncherOldenburg et al. 1997).
Under nutrient-balanced conditions, toxin production is normally low—while increased production
is associated with recovery from various types of nutrient stress. Therefore, biosynthesis of both alkaloids
(e.g., saxitoxin) and polyketides (e.g., brevetoxins) appear to be related to nitrogen and carbon metabolism
deficiency. The synthesis of PSP toxins in Alexandrium fundyense was observed to increase when the
medium is enriched in nitrogen and reduced in phosphorous. The opposite, that is, very low content of
PSP toxins, was observed when the medium was rich in phosphate and poor in nitrogen (John and Flynn
2000). Several studies support the idea that nitrogen-limiting conditions increase PSP toxin levels (Wang
et al. 2002; Frangópulos et al. 2004; Han et al. 2016). This seems to be related to the increased availability
of intracellular arginine (an important precursor for biosynthesis of PSP toxins), due to a reduced demand
of competing phosphorous-dependent pathways involved in cell division. High N:P ratios apparently
influence higher toxin production of ciguatoxin in Gamberdiscus (Chinain et al. 2010) and brevetoxin by
Karenia brevis—which is also influenced by limited-phosphorous concentration (Hardison et al. 2013).
However, the influence of enhanced phosphate supply upon toxin content is still a matter of debate. In
axenic Alexandrium tamarense-cultured in low-level phosphate conditions and supplemented with nitrate
and phosphate, toxin production was obtained when compared to the outcome under high nutrient levels
(Hu et al. 2006).
Induction or cellular accumulation of algal toxins during unbalanced growth/cell stress has become
a paradigm in attempts to understand modulation of phytoplankton toxicity by environmental factors.
Nonetheless, different patterns may extensively vary between species (Kibler et al. 2012)—and even
among strains with similar geographic distribution (Etheridge and Roesler 2005). The high degree of
variability in toxicity observed for a number of HAB species reflects the complex relationship between
environmental and genetic factors (Adolf et al. 2009; Hardison et al. 2013). Changes in total cellular
toxicity of a dinoflagellate cell, in response to environmental factors, depends upon both the absolute
toxin concentration (or the rate of production of toxin) and the relative toxin composition (Etheridge and
Roesler 2005). Some cells may exhibit higher toxicity (even when they have lower toxin concentration)
than others, depending on the established toxin profile. Alexandrium fundyense was found to have higher
toxicity (at 5ºC) owing to its toxin profile containing a higher fraction of saxitoxins and gonyatoxins, but
a lower total cell concentration at 20ºC (Etheridge and Roesler 2005).
Cellular toxicity among different isolates in laboratory cultures may be substantially lower when
compared to fresh bloom samples. Karlodinium veneficum cultivated in laboratory exhibited lower
content of karlotoxin (10 times less) than their counterparts from bloom samples; possibly culturing
conditions favor low toxin genotypes, or conditions in situ lead to enhanced toxicity (Adolf et al. 2009).
In addition, increased cellular toxicity in dinoflagellates may relate to the presence of bacteria in the
media, or via establishment of an endosymbiotic relationship (Steidinger and Baden 1984). Bacteria have
been associated with HABs events in the case of both planktonic and benthic dinoflagellates (Schweikert
and Meyer 2001); hence, truly axenic cultures of dinoflagellates are extremely difficult to obtain. The
bottom line is that bacteria may contribute to variation of toxin production, either inside the cell or secreted
to the culture medium. Some studies referred to de novo synthesis of some toxins, as shown in axenic