The small protein SCO2038 modulates tryptophan biosynthesis and morpho-physiological differentiation in Streptomyces coelicolor

In Streptomyces coelicolor small open reading frames were identified in several amino acids biosynthetic gene clusters, like SCO2038 (trpX) in the tryptophan trpCXBA locus. Here, the role of SCO2038, encoding a 63 amino acid protein, was investigated by both phenotypic and molecular analyses. A SCO2038 knockout mutant strain showed a delayed growth on minimal medium (MM), compromised actinorhodin biosynthesis and poor sporulation. The capability of this mutant to grow on MM was restored by tryptophan’s and its precursors’ supplementation. Pulldown and bacterial two hybrid assays revealed SCO2038 interaction with PepA, which is putatively involved in the metabolism of serine, glycine and cysteine. Moreover, proteomic analysis revealed a SCO2038-dependent regulation of metabolic pathways and cellular processes including tryptophan amino acid biosynthesis and the morphophysiological differentiation. Finally, a SCO2038 knockin mutant showed an increased actinorhodin production. Altogether, these findings suggest that SCO2038 modulates tryptophan biosynthesis through direct precursor availability and so exerting an effect on S. coelicolor morphophysiological differentiation