Bmp products such as Fig are persistent pollutants that accu

Bmp7 products, such as 7–9 (Fig. 2), are persistent pollutants that accumulate in the marine environment and can potentially be transferred to the human population via our trophic connections to the oceans (Wan et al., 2009). In addition to potentially addressing the mechanistic curiosities described earlier, Bmp7 can also serve as a diagnostic genetic element to mine marine (meta)genomic datasets to query the potential for natural production of polybrominated pollutants. Already, this strategy of using Bmp7 as a query element to mine complex metagenomes has led to the discovery of a biosynthetic gene clusters present in the marine sponge endosymbiotic cyanobacteria that lead to the production of 9, among other polybrominated diphenyl ethers (Agarwal et al., 2017). The cyanobacterial homolog of Bmp7 was found to be highly selective for the production of 9 using 6 as the substrate, production of other oxidative radical coupling products generated by the proteobacterial Bmp7 were not observed for the cyanobacterial Bmp7 enzyme (Agarwal et al., 2017). The widely represented oxidative radical coupling activity of CYP450 enzymes can thus have profound effects on human health via the biosynthesis of diverse natural products, ranging from lifesaving antibiotics such as 1 to persistent polybrominated environmental pollutants.
Acknowledgments
Introduction Phycotoxins are generated by certain types of phytoplankton and subsequently, accumulate in bivalve shellfishes and human through food web thereby cause a range of illness. The major phycotoxins have been categorized into seven types based on their resultant illness, including paralytic shellfish poisoning (PSP) toxins, diarrhetic shellfish poisoning (DSP) toxins, amnesic shellfish poisoning (ASP) toxins, ciguatera fish poisoning (CFP) toxins, neurotoxic shellfish poisoning (NSP) toxins, azaspiracid shellfish poisoning (AZP) toxins and clupeotoxin fish poisoning (CLP) toxins (Gerssen et al., 2010; Ajani et al., 2017). Amongst, DSP toxins are the major class of lipophilic toxins which comprise of okadaic filipin sale (OA), dinophysistoxin-1 (DTX-1), DTX-2, and other derivatives (Gerssen et al., 2010). These DSP toxins can be produced by some microalgae of the genera Prorocentrum and Dinophysis, such as Prorocentrum lima, P. concavum, P. maculosum, P. rhathymum, Dinophysis acuminata and D. fortii. It has been shown that OA is an effective inhibitor of protein phosphatases of type 1 and 2A, thereby phosphorylates several crucial proteins and consequently, cause apoptosis, cytoskeleton disruption and cell cycle alterations, etc. (Bialojan and Takai, 1988). Besides, previous studies have also demonstrated that OA exhibited embryotoxicity, neurotoxicity as well as the tumor promoting activity in cell lines (Prego-Faraldo et al., 2013; Jiao et al., 2017). In the case of bivalves, many studies have been carried out to investigate the DSP toxins induced behavioral, physiological and immunological effects (Manfrin et al., 2012; Romero-Geraldo and Hernández-Saavedra, 2014). Detoxification and elimination of DSP toxins in bivalves after exposure to OA or DSP toxins producing algae were also investigated but in much lesser extent (Suzuki et al., 2005; Manfrin et al., 2010; Rossignoli et al., 2011; Romero-Geraldo and Hernández-Saavedra, 2014; Vidal et al., 2014). It has been shown that the accumulated DSP toxins can been converted into various derivates via acylation and hydrolysis (Vale et al., 1999, 2002; Moroño et al., 2003; Torgersen et al., 2008; Manfrin et al., 2012; Prego-Faraldo et al., 2013; Reguera et al., 2014), which implied the crucial role of detoxifying enzymes, hydrolyzing enzymes, as well as antioxidant enzymes (Manfrin et al., 2012; Konoki et al., 2013; Vidal et al., 2014). Based on the changes in cytochrome P450 reductase activity during three different toxic blooms of D. acuminata and D. acuta in the Ria de Vigoy, Vidal et al. (2014) suggested that the cytochrome P450 might be involved in the OA biotransformation in Mytilus galloprovincialis. Congruently, Huang et al. (2015) found that CYP450 was significantly up-regulated in mussel gills exposed to P. lima, which corroborated the CYP450 mediated DSP toxins metabolism. However, the metabolism and detoxification mechanisms of DSP toxins in bivalve species remain obscured.