Streptomyces mobaraensis DSM40847 has been identified by genome mining and confirmed to be a new bleomycin (BLM) producer. Manipulation of BLM biosynthesis in S. mobaraensis has been demonstrated, as exemplified by the engineered production of 6'-deoxy-BLM A2, providing a biotechnology platform for BLM biosynthesis and engineering. Comparison of DNA cleavage efficiency and kinetics among 6'-deoxy-BLM A2 and selected analogues supports the wisdom of altering the disaccharide moiety to fine-tune BLM activity.