Actinobacteria are an important group of bacteria known as producers of antibiotics and other commercially interesting compounds. Unfortunately, overwhelming majority of microbial species including Actinobacteria is unculturable on synthetic media or any artificial culture conditions. To date, several bacteria are known to require specific growth factors or other diffusible components supplied by neighboring bacteria grown in the same environment. We identified coproporphyrin(Cop.)s including structurally new zincmethylphyrins I and III as growth factors for the previously uncultured bacterial strain, Leucobacter sp. strain ASN212, from a supernatant of 210 liters of Sphingopyxis sp. strain GF9 culture. Zincphyrin (Zn–Cop. III complex) is in particular a potent proliferating factor of strain ASN212 displaying the activity at picomolar level. The structure–activity relationship study for a series of transition–metal complexes of Cop. I and Cop. III revealed that Zn and Fe complexes show remarkable growth promoting activities, whereas Ni, Co or Cu–complexes did not stimulate. Focusing on the importance of Fe–Cop.III complex as an intermediate in heme biosynthesis of Actinobacteria and Firmicutes, next genomic analyses were performed. The results indicated that two heme biosynthesis genes in strain ASN212 have been truncated. As coproporphyrins are also known to generate reactive oxygen species (ROS), the requirement by strain ASN212 may play a role in the prevention of ROS accumulation in bacterial communities. In this context, our findings also demonstrated a primitive obligate mutualism existing in the bacterial communities.

Coproporphyrins, novel interphylum growth factors released by Sphingopyxis sp., enable laboratory cultivation of previously uncultured Leucobacter sp.

2019 Spring National Meeting

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