Interrogating the Tailoring Steps of Pactamycin Biosynthesis and Accessing New Pactamycin Analogues |
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| Authors: | Dr Mostafa E Abugrain Dr Wanli Lu Dr Yuexin Li Dr Jeffrey D Serrill Corey J Brumsted Andrew R Osborn Prof?Dr Adam Alani Prof?Dr Jane E Ishmael Prof?Dr Jane X Kelly Prof?Dr Taifo Mahmud |
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| Affiliation: | 1. Department of Pharmaceutical Sciences, Oregon State University, Corvallis, OR, USA;2. Veterans Affairs Medical Center, Portland, OR, USA |
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| Abstract: | Pactamycin is a bacteria‐derived aminocyclitol antibiotic with a wide‐range of biological activity. Its chemical structure and potent biological activities have made it an interesting lead compound for drug discovery and development. Despite its unusual chemical structure, many aspects of its formation in nature remain elusive. Using a combination of genetic inactivation and metabolic analysis, we investigated the tailoring processes of pactamycin biosynthesis in Streptomyces pactum. The results provide insights into the sequence of events during the tailoring steps of pactamycin biosynthesis and explain the unusual production of various pactamycin analogues by S. pactum mutants. We also identified two new pactamycin analogues that have better selectivity indexes than pactamycin against malarial parasites. |
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| Keywords: | anti-malaria biosynthesis jogyamycin natural products pactamycin Streptomyces |
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