<jats:title>Abstract</jats:title><jats:p>More and more new natural products have been found in <jats:italic>Streptomyces</jats:italic> species, which become the significant resource for antibiotics production. Among them, <jats:italic>Streptomyces lydicus</jats:italic> has been known as its ability of streptolydigin biosynthesis. Herein, we present the genome analysis of <jats:italic>S. lydicus</jats:italic> based on the complete genome sequencing. The circular chromosome of <jats:italic>S. lydicus</jats:italic> 103 comprises 8,201,357 base pairs with average GC content 72.22%. With the aid of KEGG analysis, we found that <jats:italic>S. lydicus</jats:italic> 103 can transfer propanoate to succinate, glutamine or glutamate to 2-oxoglutarate, CO<jats:sub>2</jats:sub> and L-glutamate to ammonia, which are conducive to the the supply of amino acids. <jats:italic>S. lydicus</jats:italic> 103 encodes acyl-CoA thioesterase II that takes part in biosynthesis of unsaturated fatty acids, and harbors the complete biosynthesis pathways of lysine, valine, leucine, phenylalanine, tyrosine and isoleucine. Furthermore, a total of 27 putative gene clusters have been predicted to be involved in secondary metabolism, including biosynthesis of streptolydigin, erythromycin, mannopeptimycin, ectoine and desferrioxamine B. Comparative genome analysis of <jats:italic>S. lydicus</jats:italic> 103 will help us deeply understand its metabolic pathways, which is essential for enhancing the antibiotic production through metabolic engineering.