hEDTA and EDDS as sustainable and harmless alternatives to NTA as trace metal chelators in Methanothermobacter marburgensis cultivation

The thermophilic methanogenic archaea Methanothermobacter spp. are applied as archaeal cell factories in industrial processes for methane production. Recently, secretion of commodity chemicals by M. marburgensis, such as amino acids, organic acids, or lipids has been observed. Together with the genetic tools available, genetically engineered cell factories for commodity chemical production from CO2 can be developed. However, the toxicity of the commonly used trace metal chelator Nitrilotriacetic acid (NTA) for M. marburgensis blocks potential regulatory approval for human applications. Therefore, we identified EDDS and hEDTA as suitable non-toxic alternatives as metal chelators for M. marburgensis. While EDDS reduces the specific growth rate (µ) of M. marburgensis by 40%, hEDTA shows the same µ as with NTA usage. Additionally, hEDTA offers cost wise a sustainable economic alternative to NTA with 23 € m− 3 of growth medium compared to 13 € m− 3 with NTA. With hEDTA as a harmless alternative to NTA, we are one step closer to industrial sustainable commodity chemical production from CO2 with M. marburgensis.