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

In Streptomyces coelicolor small open reading frames were identified inseveral amino acids biosynthetic gene clusters, like SCO2038 (trpX) inthe tryptophan trpCXBA locus. Here, the role of SCO2038, encoding a 63amino acid protein, was investigated by both phenotypic and molecularanalyses. A SCO2038 knockout mutant strain showed a delayed growthon minimal medium (MM), compromised actinorhodin biosynthesisand poor sporulation. The capability of this mutant to grow on MMwas restored by tryptophan’s and its precursors’ supplementation. Pulldownand bacterial two hybrid assays revealed SCO2038 interactionwith PepA, which is putatively involved in the metabolism of serine,glycine and cysteine. Moreover, proteomic analysis revealed aSCO2038-dependent regulation of metabolic pathways and cellularprocesses including tryptophan amino acid biosynthesis and the morphophysiologicaldifferentiation. Finally, a SCO2038 knockin mutantshowed an increased actinorhodin production. Altogether, these findingssuggest that SCO2038 modulates tryptophan biosynthesis through directprecursor availability and so exerting an effect on S. coelicolor morphophysiologicaldifferentiation