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Interrogating the Tailoring Steps of Pactamycin Biosynthesis and Accessing New Pactamycin Analogues
Author(s) -
Abugrain Mostafa E.,
Lu Wanli,
Li Yuexin,
Serrill Jeffrey D.,
Brumsted Corey J.,
Osborn Andrew R.,
Alani Adam,
Ishmael Jane E.,
Kelly Jane X.,
Mahmud Taifo
Publication year - 2016
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201600261
Subject(s) - biosynthesis , biochemistry , aminocyclitol , biology , chemistry , computational biology , gene , antibiotics , aminoglycoside
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.