Abstract:[Objective] To investigate the effects of deletion of an Aco-like autoregulator synthase gene, scyA1, on the physiological metabolism and regulatory network of cells, and thus to reveal the global roles of ScyA1 in cellular activities. [Methods] Dry cell weight was measured to determine the effect of scyA1 deletion on the growth of cells in liquid fermentation. Comparative RNA-Seq analysis between the scyA1 mutant and the wild type NMWT1 was performed to explore the genome-wide differentially expressed genes after 3 and 6 days of fermentation. [Results] The deletion of scyA1 did not affect the biomass of cells in liquid fermentation. After the deletion of scyA1, the expression of the genes involved in glycolysis and tricarboxylic acid cycle showed significant bidirectional differences, and the expression levels of the genes involved in the pathway from l-galactose to UDP-glucose, the pentose phosphate pathway, amino acid (l-valine, l-isoleucine, and l-tryptophan) biosynthesis, and purine nucleotide degradation were significantly upregulated. Moreover, the expression levels of a variety of gene clusters for the biosynthesis of secondary metabolites and the genes encoding conserved transcriptional regulators and mycelium structural proteins were significantly downregulated, while those of a few were significantly upregulated. [Conclusion] ScyA1 affected primary metabolism, secondary metabolism, and expression of conserved regulatory factors and mycelium structure-related genes of the test strain. The results of this study demonstrated new details of the global function of the Aco-like autoregulator synthase in Streptomyces.