Characterization of a previously uncharacterized MelC2 tyrosinase from Streptomyces griseorubiginosus and development of a whole-cell catalytic system for DOPA-melanin production

Int J Biol Macromol. 2026 May:364:152272. doi: 10.1016/j.ijbiomac.2026.152272. Epub 2026 Apr 28.

Abstract

Melanin, an important biological pigment synthesized by tyrosinase, possesses broad application potential. However, traditional production approaches have suffered from low efficiency and high cost, limiting large-scale manufacturing. To overcome these challenges, this study aimed to identify a previously uncharacterized tyrosinase (MelC2) from a melanin-producing actinomycete and establish a biocatalytic system for DOPA-melanin biosynthesis. A melanin-producing actinomycete, designated LY-1, was isolated and identified as Streptomyces griseorubiginosus based on morphology, pigment formation, and 16S rRNA phylogeny. Genomic analysis revealed a melC gene cluster encoding the tyrosinase (MelC2) and tyrosinase metallochaperone (MelC1). Phylogenetic analysis, multiple-sequence alignment, and structure prediction demonstrated that MelC2 contained six conserved histidine residues coordinating a binuclear copper center, while MelC1 possessed a signal peptide for secretion. MelC2 was heterologously expressed in Escherichia coli, purified, and biochemically characterized. The enzyme exhibited maximal activity at pH 6.0 and 40 °C, moderate pH stability, and typical Michaelis-Menten kinetics toward L-DOPA. Spectroscopic analyses (UV-Vis, FT-IR, 1H NMR) confirmed the formation of DOPA-melanin. Whole-cell catalysis was subsequently optimized by adjusting reaction temperature, pH, Cu2+ concentration, cell density, and substrate loading. Constant alkaline conditions (pH 10.0) yielded the highest DOPA-melanin production. Under optimized conditions, the engineered whole-cell system achieved a DOPA-melanin titer of 7.49 g/L. This study provides the first biochemical characterization of a previously uncharacterized tyrosinase (MelC2) from S. griseorubiginosus and establishes a whole-cell strategy for sustainable DOPA-melanin biosynthesis.

Keywords: DOPA-melanin; Tyrosinase; Whole-cell catalysis.

MeSH terms

  • Biocatalysis
  • Catalysis
  • Dihydroxyphenylalanine* / biosynthesis
  • Hydrogen-Ion Concentration
  • Kinetics
  • Levodopa* / biosynthesis
  • Melanins* / biosynthesis
  • Monophenol Monooxygenase* / chemistry
  • Monophenol Monooxygenase* / genetics
  • Monophenol Monooxygenase* / metabolism
  • Phylogeny
  • Streptomyces* / enzymology
  • Streptomyces* / genetics
  • Temperature

Substances

  • Monophenol Monooxygenase
  • Melanins
  • Dihydroxyphenylalanine
  • Levodopa