## 2 Biosynthesis of Monoterepenes in Macroalgae
### Biosynthesis of Halogenated Monoterpenes in Macroalgae  
Acyclic monoterpenes from macroalgae with bromine or chlorine atoms or both are likely the result of haloperoxidase action on either myrcene or ocimene [33; 43]. Bromonium ion-initiated cyclization was proposed to explain the formation of ochtodane ring (I-ethylidene-3,3-dimethylcyclohexane) found in marine monoterpenes [44] from myrcene. Thus, the ring closure is initiated by bromonium attack on C6-C7 olefin followed by internal addition to the resulting cationic center (Figure 3). Similar reasoning invokes ocimene as the immediate precursor of 1,3-dimethyl-I-vinylcyclohexane ring and 2,4-dimethyl-1-vinylcyclohexane ring [35]. The biogenetic schemes presented in Figure 3 are based on relevant chemical models [45; 46; 47] and successfully predict halogenation patterns and ring structures observed in the algae.  
As mentioned previously, red algae are known for their content of halogenated monoterpenes which are characterized by multiple halogen substitutions [35]. They can be produced as the consequence of conversion of GPP to myrcene with myrcene synthase followed by myrcene halogenation, with the help of haloperoxidaseases, to mono- or dihalogenated myrcene derivatives [48]. Myrcene and ocimene are immediate precursors for the formation of halogenated cyclic compounds. According to [PERSON] et al. [35], macroalgae belonging to the genus _Plocamium_, contain ocimene as the common precursor of halogenated monoterpenes, while species from _Portieria_ and _Ochtodes_ contain myrcene as the precursor of halogenated monoterpenes. However, myrcene is not the only one responsible for the biosynthesis of halogenated monoterpenes since the enzyme co-factors  
Figure 3: The scheme of cyclization of halogenated monoterpene structures.  
exhibit the key role in their synthesis. Without certain enzyme co-factors, halogenated monoterepenes could not be synthesized. [PERSON] et al. (2019) demonstrated that _Ochtodes secundiramea_ ([PERSON]) [PERSON] was not able to synthesize halogenated monoterepenes without the presence of bromide and vanadate which are bromoperoxidase co-factors. This was also confirmed by [PERSON] and [PERSON] [PERSON] and [PERSON] (2019) when they removed bromide and vanadate from the medium of _O. secundiramea_ and consequently bromoperoxidase-catalyzed halogenation did not occur which indicated that bromide and vanadate are required for the biosynthesis of brominated and bromochlorinated monoterepenes in _O. secundiramea_. Furthermore, it was found that _Portieria horemannii_ ([PERSON]) [PERSON]. [PERSON] contains only chlorinated monoterepenes, while _Ochtodes secundiramea_ does not, which indicates the variations in halogenation enzyme activity ([PERSON] et al., 2019). Moreover, it could not be said for certain that the cyclization of myrcene to ochtodane and other related structures is catalyzed by the enzymes. [PERSON] (2019) showed that the cyclization can occur without the enzyme catalysis in the presence of bromonium ion, while [PERSON] and [PERSON] and [PERSON] (2019) showed that _P. horemannii_ possess chlorination enzyme which does not require bromonium ion intermediate. [PERSON] and [PERSON] [PERSON] and [PERSON] (2019) proposed that halogenation of monoterepenes is the consequence of Markovnikov addition of the halogen to the olefinic bond of myrcene which is attacked by the halonium ions.