Trichlorination of l-Leucin by Fe(II) Halogenases

Significance

Barbamide 1 was isolated from marine bacterium Lyngbya majuscule (J. Orjala et al. J. Nat. Prod. 1996, 59, 427-430). It shows some activity as molluscicidal agent. Trichlorination of unactivated carbon centers cannot be achieved easily. Herein, l-[¹⁴C]Leu-S-BarA (2) or monohalogenated 3 were transformed to dichloroleucine 4 with BarB2 in the presence of O₂, chloride and α-ketoglutarate (α-KG). Incubating this mixture with BarB1 gave trichlorinated product 5. These two enzymes complement each other; employing only one of them or adding them in the opposite order did not yield the desired product. Peptidyl carrier protein and nonheme Fe(II) halogenases BarB1and BarB2 could be produced from E. coli.