Abstract
The bleomycins (BLMs) belong to a subfamily of glycopeptide antibiotics and are clinically applied in combination chemotherapy regimens to treat various malignancies. But the therapeutic applications of BLMs are restricted by the accompanied dose-dependent lung toxicity and potential incidence of lung fibrosis. Many efforts have been devoted to develop novel BLM analogues, for seeking of drug leads with improved antitumor activity and/or reduced lung toxicity. The progresses in the biosynthetic studies of BLMs have greatly expedited the process to achieve such goals. This review highlights the discovery and development of microbial BLM analogues in the past two decades, especially those derived from engineered biosynthesis. Moreover, the summarized structure-activity relationship, which is specifically focusing on the sugar moiety, shall shed new insights into the prospective development of BLM analogues.
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Funding
This work was supported in part by grants from the National High Technology Research and Development Program of China 2012AA02A705, the Chinese Ministry of Education 111 Project B0803420, National Major Scientific and Technological Special Project 2011ZX09401-001, US NIH grant CA94426, and the Natural Products Library Initiative at TSRI.
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Kong, J., Yi, L., Xiong, Y. et al. The discovery and development of microbial bleomycin analogues. Appl Microbiol Biotechnol 102, 6791–6798 (2018). https://doi.org/10.1007/s00253-018-9129-8
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DOI: https://doi.org/10.1007/s00253-018-9129-8