Iodide (I⁻) and bromide (Br⁻) are actively taken up from seawater and (i) may directly undergo halogenation into monosubstituted halomethanes, or (ii) are oxidized respectively as HOI and HOBr by extracellular vanadium-dependent haloperoxidases (V-HPOs) which use photosynthetic hydrogen peroxide on a routine basis, and peroxide generated by oxidative burst under stress conditions, as discussed further. In the first instance, the biosynthesis of methyl bromide and methyl iodide involves the transferase - mediated nucleophilic attack of corresponding halides at the electrophilic CH₃⁺S site of S-Adenosyl Methionine (SAM; Figure 1), but is clearly limited to monohalogenation [9,10], i.e., the production of CH₃I and CH₃Br (Figure 2 (a). In the second case, methylation can produce di- and polysubstituted halomethanes, including a variety of hetero-substituted forms (e.g., CHBr₂I; Figure 2 (b)) as in Cystoseira barbata [11]. Electrophilic reaction of I⁺ and especially Br⁺ with acceptors (centers of high electron density in e.g., enols, phenolics and phloroglucinol derivatives) can be rationalized on the basis of rearrangement of the double-bond. Hence a plausible mechanism is the successive bromination of the enols of C₂ or C₃ etc. units containing C=O groups followed by the loss of C₁ (CH₂O from CH₃CHO and CH₃CHO from CH₃.CO.CH₃ with concomitant formation of e.g., CH₂Br₂ and CHBr₃ [10–12]. Whatever their origin (i.e., by cationoid or anionoid halogenation), volatile halogenated organic compounds (VHOCs) globally predominate in brown kelp effluxes and ensure a fast disposal of the ROS detoxification products (HOI and HOBr) while conceivably regulating apoplastic iodine and bromine reserves (see below). Furthermore, excess HOI and HOBr resulting from vanadium-dependant bromoperoxidase (V-BrPO) upregulation under oxidative stress is thought to complement on site destruction of microbial infection by ROS, and prevent microbial biofilm formation [13] or modulate its architecture (La Barre, unpubl. results), while VHOCs would help discourage reinfection.

Non-volatile iodine is mainly concentrated from seawater in the peripheral tissues of brown algae [15]. In Laminariales, several speciation studies have concluded that up to 90% of total iodine is mainly stored in a labile inorganic form identified as iodide [16–19], while its organic forms in Laminaria are dominated by hormone-like tyrosine derivatives, i.e., monoiodotyrosine or MIT (10–15 ppm), diiodotyrosine or DIT (20–25 ppm), shown in Figure 3. The ubiquity of iodinated tyrosines (e.g., MIT, DIT) across extant eukaryotic phyla has shown their general function as endocrine molecules involved in cell-cell communication (plants) as well as time-coordinated and dose-dependent developmental changes, as reviewed by [20]. Trophic transfers of thyroxin (TH) and thyroid hormone precursors from primary producers (possibly detected in phytoplankton upon immunological assays) to consumers are essential to the metamorphosis of larvae of marine invertebrates [21] and gene regulation and signal transcription in vertebrates. Contrary to most organohalogenates of phaeophyte origin, tyrosin halogenations into MIT and DIT is believed to occur spontaneously, i.e., they are not enzyme mediated [22]. The facile halogenation of MIT and DIT and the emphasis on the signaling role of these ubiquitous metabolites in eukaryotic physiology [20] makes them possible candidates as hormone-like substances, along with known elicitors (alginate hydrolysates) of kelps [23].

Phloroglucinol and derived products are essentially plant products. Singh and Bharate [24] conveniently separates them into phloroglucinols (mono-, di-, tri-, tetra- and oligomeric) and phlorotannins. According to this classification, only a few phloroglucinols have been isolated from macrophytic algae, whereas phlorotannins are exclusively found in brown algae and are regarded as the functional equivalents of terrestrial tannins. Halogenated monomeric phenolics are also occasionally found in brown algae, as well as in a few red algae.

In brown algae, the overall composition in saturated and unsaturated fatty acids is equivalent to that found in red algae, with a high proportion of C18 and C20 polyunsaturated forms (PUFA). Three chlorinated oxylipins were isolated from the Laminariale Egregia menziesii (Alariaceae) by Todd et al. [41], two originating from the C18 PUFA stearidonic acid (egregiachloride A and B, Figure 6a) and one from the C20 PUFA eicosapentaenoic acid (egregiachloride C, Figure 6b).

Kousaka et al. [42] isolated six halogenated (eiseniachlorides) or iodinated (eiseniaiodides) species among a whole series of C18 oxylipins from another Alariaceae, Eisenia bicyclis, also biosynthesized from a stearidonic acid precursor. Along with eiseniachloride A and B and eiseniaiodide A and B, two cyclization variants (Figure 7), were determined by extensive 2-D NMR analysis. Interestingly, the halogenation (via C13 HPOTE resulting from LOX i.e., lipoxygenase oxidation) occurs inside the cell and does not include brominated forms. Finally, a C20 form (via addition of an ethylene group) was determined as eiseniachloride C. Anti bacterial assays on Bacillus subtilis and on Staphylococcus aureus did not shown any improvement of the activities of any of the halogenated forms over the non-halogenated ones [42]. Ecklonialactones A and B are potential feeding repellents against predating abalone seashell, but no mention is made of this ecological role for their halogenated forms [42].

Similar to plants, in the brown alga Saccharina (formerly Laminaria) angustata, the LOX-derived fatty acid hydroperoxides can be further cleaved to form C-6 (derived from C18 PUFA) and C-9 aldehydes (derived from C20 PUFA) none of which have been reported under halogenated forms (see review [43]). Although chlorosulpholipids have been reported in a number of freshwater algae, there is no evidence that they occur in marine algae [44].

The only phaeophycean halogenated nor-sesquiterpenes were isolated from Padina tetrastromatica [45], possibly oxidation forms of perhydrolinalool. An atypical iodinated meroterpene (terpene with an aromatic moiety) has been characterized in Ascophyllum nodosum by Arizumi et al. [46]. This is in sharp contrast to red algae, in which secondary metabolites structures are abundant (over 1,200 structures in 2005), with highly diverse halogenated terpenes (over 800 chlorinated and/or brominated forms many of which have attracted the interest of pharmacologists [47]), and which probably reflect a capacity to diversify their defense strategies which is not encountered in brown algae.

If sulfatation of carbohydrates is a common feature in brown algae that confers them with specific physical and eco-physiological properties [48], there has never been any report of halogenated polysaccharides, in contrast to polyphenols in which either substitution (sulfates or halogen) can be found.

The element iodine has been discovered in the ashes of brown algal kelps in the beginning of the 19th century. The kelp Laminaria digitata presents an average iodine content of 1.0% of dry weight, representing a ca. 30,000-fold accumulation of this element from seawater [70]. In this brown alga, micro-chemical imaging of iodine distribution reveals an unexpected sub-cellular distribution in the cell walls of peripheral cells [15], with the predominance of iodide species [71]. Although L. digitata represents one of the most studied models, the biochemical pathways leading to this very efficient iodide trapping and the mechanism responsible for its release into the surroundings are still speculative. Specific oxidation processes are essential in both the mechanisms of iodine uptake and release. In L. digitata, iodine is thought to be taken up by a mechanism based on the haloperoxidase-mediated oxidation of iodide, a mechanism which requires a constitutive apoplastic level of hydrogen peroxide of circa 50 μM [70] and which could involve an apoplastic V-IPO [60,72]. Recent studies [15,69] have shown that iodide is mainly chelated by apoplastic macromolecules. Such a storage mechanism should provide an abundant and accessible source of reduced iodine, which can be easily remobilized for potential anti-oxidative activities and chemical defense. This unique setup has never been described among all living systems. However, in the presence of exogenously-added 2 mM H₂O₂, a net efflux of iodide was observed [70]. Yet there is no clear answer as to why Laminariales have developed (or retained?) such an important and extensive metabolic dependence to iodine, as compared to most halogen-using marine life forms [71].

The molecular mass of iodine (126.90 U) is the highest by far of all elements used in biological systems, including metals. The prevalence of iodine chemistry in very early life forms has recently led to interesting speculations as its cornerstone role as a catalyst and inorganic antioxidant [20] without which the emergence of multicellularity would never have taken place. Indeed, iodine is regarded as an additional biomarker towards the presence of life in extraterrestrial environments. Early prokaryotes (LUCA) had to carry out the conversion of toxic environmental iodate into iodine which could be readily incorporated in the cytoplasm and perform a number of essential catalytic functions, e.g., by coupling with essential organic molecules. The reducing (electron loosing) capacity of halides being proportional to the atomic size of the halogen, the oxidation products of active oxygenated species (AOS) and iodide occur almost readily as compared to bromine or chlorine. Iodine production by iodoperoxidases in several phaeophyte taxa, e.g., several Laminariales, represent a very efficient way of quenching excess hydrogen peroxide and reactive oxygenated radicals, following oxidative burst, or simply accumulating in plastids from regular photosynthesis [71]. An equivalent functional (primary) role is assigned to highly nucleophilic phlorotannins which are produced in a number of shore Fucales, following seasonal patterns in western Brittany (France), especially during summer with longer exposures to sunlight, and at mid-tide levels [73]. Interestingly, it was shown that the average iodine contents were lowest in summer months (0.25–0.60% dry weight) and highest in late autumn and in winter (in the range 0.75–1.20% dry weight) in the kelp Laminaria digitata [74]. Taken together, these data may help understand how the two classes of compounds interplay as ROS quenchers. However, in L. digitata, soluble phlorotannins are very low [73] and therefore iodide is likely to play a major role as an antioxidant [71]. Further studies are required in other species of Laminariales and of Fucales in order to understand the respective roles and the possible alternation between phlorotannins and iodide. Within-thallus translocation has long been documented in red and various brown algae, the sieve elements in both lineages lacking the vascularized phloem structure of higher plants [75]. In Laminariales, translocation of carbon labeled photosynthates from older parts of the frond towards the meristematic region and to the holdfast haptera has been demonstrated [76]. Mannitol, malate, citrate, polar amino acids and proteins are non-selectively translocated via the sieve tube of Macrocystis pyrifera, as well as inorganic cations (K⁺, Na⁺, Mg²⁺ and Ca²⁺) and anions among which chloride and bromide [77]. Iodide was later found to translocate in a source-to-sink manner, compatible with known distribution of this element in Laminariales [78]. As of now, organic halides have not been identified as translocates, yet there are strong suspicions that regulation of V-HPO genes operates within the context of a systemic response [61]. Systemy would operate either externally (detection in the water column of an eliciting signal generated in a stressed region of the thallus by a naïve region of the same individual, followed by a defense response), or internally via translocation. It could involve halogenated compounds (VHOC) or oxygenated species (aldehydes) which are produced as defense compounds in plantlets of L. digitata which are metabolically challenged [79,80] and thus are possible pheromone-like candidates, along with known elicitors (alginate hydrolysates) of this particular kelp.

Iodine species are present in the marine boundary layer (MBL) due to the release of I₂ and of photo-labile iodocarbons from macro- and micro-algae (Figure 10). Whilst the primary source of inorganic chlorine and bromine species in the remote ocean is likely to be their release from the significant seasalt halide reservoir in atmospheric aerosol, the direct emission of halocarbons [81,82] from intertidal macroalgal species [79], from phytoplankton [83] and from biogenic marine aggregates [84] has been well established and contributes significantly to the coastal atmospheric burden of Reactive Halogen Species (RHS) [81,82]. Indeed shallow coastal areas where kelp beds of Laminaria digitata correspond to hotspots of biogenic halocarbon emission have been recently investigated with particular attention to iodine speciation. In particular, CH₂I₂ is the dominant organic iodine species released from kelps [81,82] and has it been suggested as one of the initiators of the iodine nanometric particles that function as cloud-forming nuclei [85]. The most widely-observed coastal inorganic RHS, iodine monoxide (IO), has also consistently been shown to exhibit a tidal signature, but only during daytime, consistent with photochemical formation of IO. In addition to the tidal halogen cycling, studies at Mace Head in Western Ireland revealed the rapid appearance of high concentrations of ultrafine aerosol particles at daytime low tide [86,87]. Should even a small fraction of the particles grow sufficiently large that they would act as Cloud Condensation Nuclei (CCN) at supersaturations corresponding to updraughts in typical marine stratocumulus clouds, such particle formation may significantly impact on local and regional radiative forcing and climate.

During the 2006 coastal campaign of the Reactive Halogens in the Marine Boundary Layer (RHaMBLe) project in Roscoff in Western France [88], it was clearly demonstrated that iodine-mediated coastal particle formation occurs, driven by daytime low tide emission of molecular iodine (I ₂), by macroalgal species fully or partially exposed by the receding waterline. Ultrafine particle concentrations strongly correlate with the rapidly recycled reactive iodine species, IO, produced at high concentrations following photolysis of I₂. The heterogeneous macroalgal I₂ sources lead to variable relative concentrations of iodine species observed by path-integrated [89] and in situ measurement techniques [90]. As shown at Roscoff, rockweed (the fucoid alga A.nodosum) beds may also emit more constantly than kelps because there are exposed to air more frequently (even during small tides) and for longer periods of time [91,92]. However, it was also observed at Cape Grim in Australia, that the contribution to particle formation of the fucoid alga Durvillaea potatorum is very limited because this alga does not release I₂ [93]. These discrepancies have been tentatively explained by different capabilities of accumulation and emission between these two orders of large brown algae [92]. The evolution of new biochemical adaptations using more specific V-HPO has probably contributed to a better capacity to oxidize iodine and to use halides in kelps. In Laminariales (see section 2), iodoperoxidases activities that are specific for iodide, have been localized at least partly extracellularly in the apoplasm [60,94] and may explain the very high amount of iodide accumulated in their cell walls and higher efficiency of kelps for iodine oxidation, even in the absence of strong external oxidants, such as ozone. Ascophyllum nodosum was shown to possess two distinct isoforms of V-BrPO, one of them being located very superficially at the thallus surface [95] which is likely conferring a better capacity to oxidize iodide leading to high I₂ emissions. Interestingly, this agree with the modeling of I₂ emissions in the Roscoff area during the RHaMBLe project [92], which showed that the occurrence of rockweed in the mid-littoral zone of sheltered habitats complements efficiently the presence of large stands of Laminariales.

V-BrPOs still operate at 70 °C, in up to 60% organic solvents, they resist detergents, and maintain constant activity throughout the catalytic cycle (vanadium remains at VV oxidation state). This structural and functional resilience makes them all the more attractive as potential biocatalysts [52]. In addition, this particular enzyme is capable in vitro of carrying out sulfoxidation reactions enantioselectively on methyl phenyl substrate [99]. As biocatalysts of underwater “soft” or flexible adhesives, V-HPOs offer a very interesting alternative to “hard” or cementing biopolymers used by barnacles and many rock-dwelling molluscs. Bacterial haloperoxidases have been revealed by recent genomic studies. The chemistry of prokaryotic haloperoxidases may show new biological functions and thus greatly extend the potential of these enzymes as biocatalysts operating on novel and suitably selected organic substrates. In this area of research with potential impacts in the biosynthesis of marine natural products, it is very likely that structural biology and biotechnology will lead to important breakthroughs toward environment-friendly chemistry. To this end, methods such as exon shuffling for the directed evolution of bacterial and possibly algal enzymes will be employed.