Isolation and Biosynthesis of an Azoxyalkene Compound Produced by a Multiple Gene Disruptant of Streptomyces rochei

Streptomyces rochei 7434AN4 predominantly produces lankacidin and lankamycin under normal culture conditions, thus suggesting that other biosynthetic gene clusters for secondary metabolites are silent. To identify the silent metabolites of 7434AN4, we constructed mutant KA57 with multiple disruptions of the transcriptional repressor srrB and the biosynthesis genes for both antibiotics. KA57 accumulated a compound (KA57A) with a strong UV absorption at 235 nm, not detected in the parent strain or other mutants. Various spectroscopic analyses revealed that KA57A is an azoxyalkene compound with the molecular formula C10H20N2O3 and with the R configuration at C-2. Biosynthesis of KA57A was also studied by feeding with labeled acetates, amino acids, and 1-hexylamine. The hexenyl moiety (C1'-C6') was derived from fatty acid, whereas the 3-aminobutan-1,2-diol moiety (C1-C4) was derived from C-2 of acetate (C1) and serine (C2-C4). Incorporation of [1,1-H-2(2)]1-hexylamine indicated that C1'-C2' dehydrogenation occurs as the final step of biosynthesis.