TABLE 2.
Enzymatically produced alkaloids from halogenated substrates.
| Halogen | Halogenated substrate | Derivatized compound(s) detected | Chassis | References |
| Monoterpene indole alkaloids | ||||
| Fluorine | 4-, 5-, 6-, 7-fluoroindole | Tryptophan | In vitro | Smith et al., 2014 |
| 4-fluorotryptophan | Tryptamine | In vitro | McDonald et al., 2019 | |
| 5-fluorotryptamine | Serpentine, ajmalicine, yohimbine, vindolidine, vindoline, catharanthine | C. roseus | Mccoy and O’connor, 2006 | |
| 5-fluorotryptamine | Strictosidine | In vitro | Loris et al., 2007 | |
| 5-fluorotryptamine | Ajmalicine, tabersonine, serpentine, catharanthine | C. roseus | Runguphan et al., 2009 | |
| 6-fluorotryptamine | Serpentine, ajmalicine, yohimbine, akuammicine, vindolidine, catharanthine, | C. roseus | Mccoy and O’connor, 2006 | |
| 6-fluorotryptamine | Strictosidine | In vitro | Loris et al., 2007 | |
| 4-fluorotryptamine | Strictosidine, strictosidine aglycone, canthemine | In vitro | McCoy et al., 2006 | |
| 5-, 6-, 7-fluorotryptamine | Strictosidine, strictosidine aglycone | In vitro | McCoy et al., 2006 | |
| 10-, 11-fluorostrictosidine | Strictosidine aglycone | In vitro | Yerkes et al., 2008 | |
| Chlorine | 4-, 5-, 6-, 7-chloroindole | Tryptophan | In vitro | Smith et al., 2014 |
| 4-, 5-, 6-, 7-, (5,6)-(di)chlorotryptophan | Tryptamine | In vitro | McDonald et al., 2019 | |
| 5-chloro-L-tryptophan | Tryptamine, strictosidine, tabersonine, ajmalicine, catharanthine | C. roseus | Runguphan et al., 2010 | |
| 7-chloro-L-tryptophan | Tryptamine, strictosidine, dihydroakuamicine, | C. roseus | Runguphan et al., 2010 | |
| 5-chlorotryptamine | Strictosidine | C. roseus | Bernhardt et al., 2007 | |
| 5-chlorotryptamine | Ajmalicine, catharanthine, tabersonine, strictosidine, cathenamine, serpentine, isositsirikine | C. roseus | Runguphan and O’Connor, 2009 | |
| 7-chlorotryptamine | Dihydroakuammicine | C. roseus | Runguphan and O’Connor, 2013 | |
| 6-chlorotryptophan | Tryptamine | N. benthamiana | Fräbel et al., 2016 | |
| 7-chlorotryptophan | Tryptamine | N. benthamiana | Fräbel et al., 2016 | |
| 6-chlorotryptamine | Dihydroakuamicine, akuammicine, tabersonine | C. roseus | Runguphan and O’Connor, 2013 | |
| Bromine | 4-, 5-, 6-, 7-bromoindole | Tryptophan | In vitro | Smith et al., 2014 |
| 4-, 5-, 6-, 7-bromotryptophan | Tryptamine | In vitro | McDonald et al., 2019 | |
| 7-bromo-L-tryptophan | Dihydroakuammicine | C. roseus | Runguphan et al., 2010 | |
| 5-bromotryptamine | Strictosidine, ajmalicine, yohimbine, akuammicine | C. roseus | Bernhardt et al., 2007 | |
| 5-bromotryptamine | Ajmalicine, strictosidine, serpentine, isositsirikine | C. roseus | Runguphan and O’Connor, 2009 | |
| 7-bromotryptamine | Dihydroakuammicine | C. roseus | Runguphan and O’Connor, 2013 | |
| Iodine | 7-iodoindole | Tryptophan | In vitro | Smith et al., 2014 |
| 5-, 7-iodotryptophan | Tryptamine | In vitro | McDonald et al., 2019 | |
| Benzylisoquinoline alkaloids | ||||
| Fluorine | 2-(4-(trifluoromethoxy)phenyl)acetaldehyde, 2-(2-fluorophenyl)acetaldehyde, 2-(3-fluorophenyl)acetaldehyde, 2-(4-fluorophenyl)acetaldehyde | Norcoclaurine | In vitro | Ruff et al., 2012 |
| 3-(4-trifluoromethylphenyl)-1-propylaldehyde | Norcoclaurine | In vitro | Nishihachijo et al., 2014 | |
| 4−fluorophenylacetaldehyde | Norcoclaurine | In vitro | Pesnot et al., 2012 | |
| 3-fluoro-L-tyrosine | L-DOPA, tyramine, dopamine, norcoclaurine | In vitro | Wang et al., 2019b | |
| 3-fluoro-L-tyrosine | L-DOPA, dopamine, norcoclaurine, methylcoclaurine, reticuline | S. cerevisiae | Li et al., 2018 | |
| Chlorine | 3-chloro-L-tyrosine | Dopamine | In vitro | Wang et al., 2019b |
| 3-chloro-L-tyrosine | L-DOPA, dopamine, norcoclaurine, methylcoclaurine, reticuline | S. cerevisiae | Li et al., 2018 | |
| Bromine | 4−bromophenylacetaldehyde | Norcoclaurine | In vitro | Pesnot et al., 2012 |
| 2-bromophenylacetaldehyde | Norcoclaurine | In vitro | Wang et al., 2019b | |
| para-bromo-meta-L-tyrosine | Dopamine | In vitro | Wang et al., 2019b | |
| Iodine | 3-iodo-L-tyrosine | Dopamine | In vitro | Wang et al., 2019b |
| 3-iodo-L-tyrosine | L-DOPA, dopamine, norcoclaurine, methylcoclaurine, reticuline | S. cerevisiae | Li et al., 2018 | |
A tabulated summary of studies reporting enzymatic synthesis, using wild type or engineered enzymes, of new-to-nature MIAs and BIAs from halogenated substrates. Information is provided on the nature of the halogenated substrate, the natural scaffold of which halogenated derivatives were detected, and chassis in which the conversions were established.