Amycolatopsis regifaucium, a Gram-positive actinomycete, is a prolific source of biologically active compounds, including polyphenol antibiotics like kigamicins. This study presents the draft genome of Amycolatopsis regifaucium DSM 45072T (= GY080T), which spans 8.28 Mbp and is assembled into 62 contigs, with annotation revealing 312 subsystems, 7,966 coding genes, and 52 RNAs, with a GC content of 68.5 mol%. We found a significant genomic diversity within the genus, revealing variations in core and accessory genomic elements across species. Multiple biosynthetic gene clusters (BGCs) have been identified, including a previously unidentified glycopeptide antibiotic (GPA) gene cluster and a type II polyketide synthase (PKS) gene cluster, highlighting the organism's metabolic versatility and potential for the biosynthesis of novel natural products. Our analysis confirmed the production of decaplanin, an antibiotic previously attributed to Amycolatopsis decaplanina DSM 44594T. Correspondingly, the gene cluster responsible for decaplanin biosynthesis is identified in A. regifaucium DSM 45072T and A. decaplanina DSM 44594T. Additionally, a putative type II PKS gene cluster is predicted within the glycopeptide antibiotic-producing clade (Cluster A) of the genus Amycolatopsis. Genomics insights from Amycolatopsis regifaucium DSM 45072T represent it as a promising genetic resource with significant implications for biotechnological and pharmaceutical innovation, particularly in discovering and developing novel antimicrobial agents.