<i>De novo</i> production of eumelanin in a fermentative process with <i>Corynebacterium glutamicum</i>

Melanin, a versatile and valuable pigment with diverse industrial applications, has attracted significant interest owing to its unique properties ranging from UV protection to antioxidant capabilities. Despite its potential, traditional methods of melanin production often face challenges related to scalability and environmental impact. Available microbial production systems, which offer sustainability, commonly pose issues related to safety, productivity, cost-effectiveness. Here we present a safe and cost-effective microbial production system with the industrial workhorse <i>Corynebacterium glutamicum</i> to overcome the limitations of current production strategies. Here, melanin production was achieved in a chemically defined medium directly from glucose circumventing the addition of its precursor l-tyrosine, which reduced the reliance on complex and expensive substrates. The produced pigment displayed properties that highly resembled that of eumelanin when analyzed using HPLC, UV-visible spectrophotometry, FTIR, and SEM. Guided by model-based optimization, a melanin titer of 1.03 g/L was reached in shake flasks. Finally, this fermentative production was scaled-up in a 6-L bioreactor and its potential for bio manufacturing was demonstrated. Melanin titer was only 0.32 ± 0.04 g/L after 72 h, which was lower than the titer obtained in shake flasks. This reduction was likely due to limited l-DOPA oxidation under the bioreactor operation conditions.