Streptomyces albus J1074 is a derivative of the S. albus G1 strain defective in SalG1 restriction-modification system. Genome sequencing of S. albus J1074 revealed that the size of its chromosome is 6.8 Mb with unusually short terminal arms of only 0.3 and 0.4 Mb. Here we present our attempts to evaluate the dispensability of subtelomeric regions of the S. albus J1074 chromosome. A number of large site-directed genomic deletions led to circularization of the S. albus J1074 chromosome and to the overall genome reduction by 307 kb. Two spontaneous mutants with an activated carotenoid cluster were obtained. Genome sequencing and transcriptome analysis indicated that phenotypes of these mutants resulted from the right terminal 0.42 Mb chromosomal region deletion, followed by the carotenoid cluster amplification. Our results indicate that the right terminal 0.42 Mb fragment is dispensable under laboratory conditions. In contrast, the left terminal arm of the S. albus J1074 chromosome contains essential genes and only 42 kb terminal region is proved to be dispensable. We identified overexpressed carotenoid compounds and determined fitness costs of the large genomic rearrangements.