Adenine N⁶-substituent of agrocin 84 determines its bacteriocin-like specificity

Abstract

AGROCIN 84 (Fig. 1(1)) is the active factor¹ in the biological control of crown gall, a plant cancer induced by certain strains of Agrobacterium. Growth inhibition by agrocin 84 has been correlated with pathogenicity^2–5 and the presence of a nopaline (N²-(1,3-dicarboxypropylarginine)) tumour-inducing plasmid^3–5. Characterisation of agrocin 84 as a disubstituted adenine nucleotide⁶ has been reported and a proposed⁷ peptide structure has been retracted⁸. What are those salient features of agrocin 84 that determine its remarkable bacteriocin-like specificity towards cancer-inducing strains of Agrobacterium? The structural evidence reported here shows that a 5′-phosphoryl linkage from the ‘fraudulent’ nucleoside core 9-(3′-deoxy-β-D-threo-pentofuranosyl) adenine⁶ to the amide group of D-threo-2,3-dihydroxy-4-methylpentanamide (Fig. 1(6)) is required for antibiotic activity, but bacteriocin-like specificity is conferred by a D-glucofuranosyloxyphosphoryl substituent at N⁶ of adenine. Agrocin 84 seems to be the harbinger of a series of highly specific nucleotide bacteriocins, which behave as molecular ‘Trojan horses’.