Heterologous expression of the biosynthetic gene clusters of coumermycin A 1 , clorobiocin and caprazamycins in genetically modified Streptomyces coelicolor strains

The biosynthetic gene clusters of the aminocoumarin antibiotics clorobiocin and coumermycin A 1 and of the liponucleoside antibiotic caprazamycin were stably integrated into the genomes of different host strains derived from Streptomyces coelicolor A3(2). For the heterologous expression of clorobiocin derivatives in a chemically defined medium, inclusion of 0.6% of the siloxylated ethylene oxide/propylene oxide copolymer Q2‐5247 into the growth medium proved to result in a 4.8‐fold increase of productivity. Presumably, this copolymer acts as an oxygen carrier. The additional inclusion of cobalt chloride (0.2–2 mg l −1 ) dramatically increased the percentage of the desired compound clorobiocin within the total produced clorobiocin derivatives. This is very likely due to a stimulation of a cobalamin‐dependent methylation reaction catalyzed by the enzyme CloN6 of clorobiocin biosynthesis. All three investigated host strains ( S. coelicolor M512, M1146 and M1154) gave similar production rates of total clorobiocin derivatives (on average, 158 mg l −1 in the presence of 0.6% Q2‐5247 and 0.2 mg l −1 CoCl 2 ). In contrast, heterologous production of caprazamycin derivatives was optimal in strain M1154 (amounts of 152 mg l −1 on average). © 2010 Wiley Periodicals, Inc. Biopolymers 93: 823–832, 2010.