Interrogating the Tailoring Steps of Pactamycin Biosynthesis and Accessing New Pactamycin Analogues.
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.
Department of Pharmaceutical Sciences, Oregon State University, Corvallis, OR, 97331-3507, USA.
Mostafa E
ME
Abugrain
Department of Pharmaceutical Sciences, Oregon State University, Corvallis, OR, 97331-3507, USA.
Wanli
W
Lu
Veterans Affairs Medical Center, Portland, OR, 97239, USA.
Yuexin
Y
Li
Department of Pharmaceutical Sciences, Oregon State University, Corvallis, OR, 97331-3507, USA.
Jeffrey D
JD
Serrill
Department of Pharmaceutical Sciences, Oregon State University, Corvallis, OR, 97331-3507, USA.
Corey J
CJ
Brumsted
Department of Pharmaceutical Sciences, Oregon State University, Corvallis, OR, 97331-3507, USA.
Andrew R
AR
Osborn
Department of Pharmaceutical Sciences, Oregon State University, Corvallis, OR, 97331-3507, USA.
Adam
A
Alani
Department of Pharmaceutical Sciences, Oregon State University, Corvallis, OR, 97331-3507, USA.
Jane E
JE
Ishmael
Veterans Affairs Medical Center, Portland, OR, 97239, USA.
Jane X
JX
Kelly
Department of Pharmaceutical Sciences, Oregon State University, Corvallis, OR, 97331-3507, USA. taifo.mahmud@oregonstate.edu.
Taifo
T
Mahmud
D000903:Antibiotics, Antineoplastic / Q000096:biosynthesis* / Q000737:chemistry; D008968:Molecular Conformation; D010142:Pactamycin / Q000031:analogs & derivatives* / Q000096:biosynthesis* / Q000737:chemistry; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism*
D000903:Antibiotics, Antineoplastic; D010142:Pactamycin
Streptomyces; anti-malaria; biosynthesis; jogyamycin; natural products; pactamycin