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- W2611907400 abstract "The increasing prevalence of polymyxin-resistant bacteria has stimulated the search for improved polymyxin lipopeptides. Here we describe the sequence and product profile for polymyxin D nonribosomal peptide synthetase from Paenibacillus polymyxa ATCC 10401. The polymyxin D synthase gene cluster comprised five genes that encoded ABC transporters (pmxC and pmxD) and enzymes responsible for the biosynthesis of polymyxin D (pmxA, pmxB, and pmxE). Unlike polymyxins B and E, polymyxin D contains d-Ser at position 3 as opposed to l-α,γ-diaminobutyric acid and has an l-Thr at position 7 rather than l-Leu. Module 3 of pmxE harbored an auxiliary epimerization domain that catalyzes the conversion of l-Ser to the d-form. Structural modeling suggested that the adenylation domains of module 3 in PmxE and modules 6 and 7 in PmxA could bind amino acids with larger side chains than their preferred substrate. Feeding individual amino acids into the culture media not only affected production of polymyxins D1 and D2 but also led to the incorporation of different amino acids at positions 3, 6, and 7 of polymyxin D. Interestingly, the unnatural polymyxin analogues did not show antibiotic activity against a panel of Gram-negative clinical isolates, while the natural polymyxins D1 and D2 exhibited excellent in vitro antibacterial activity and were efficacious against Klebsiella pneumoniae and Acinetobacter baumannii in a mouse blood infection model. The results demonstrate the excellent antibacterial activity of these unusual d-Ser3 polymxyins and underscore the possibility of incorporating alternate amino acids at positions 3, 6, and 7 of polymyxin D via manipulation of the polymyxin nonribosomal biosynthetic machinery." @default.
- W2611907400 created "2017-05-12" @default.
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- W2611907400 date "2017-05-02" @default.
- W2611907400 modified "2023-10-17" @default.
- W2611907400 title "Characterization of the Polymyxin D Synthetase Biosynthetic Cluster and Product Profile of <i>Paenibacillus polymyxa</i> ATCC 10401" @default.
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- W2611907400 cites W1502350431 @default.
- W2611907400 cites W1521878726 @default.
- W2611907400 cites W1546849601 @default.
- W2611907400 cites W1587696955 @default.
- W2611907400 cites W1894518760 @default.
- W2611907400 cites W1957185080 @default.
- W2611907400 cites W1965811910 @default.
- W2611907400 cites W1966524255 @default.
- W2611907400 cites W1967869305 @default.
- W2611907400 cites W1970386034 @default.
- W2611907400 cites W1973223043 @default.
- W2611907400 cites W1973383468 @default.
- W2611907400 cites W1979973356 @default.
- W2611907400 cites W1980136131 @default.
- W2611907400 cites W1981160369 @default.
- W2611907400 cites W1987171993 @default.
- W2611907400 cites W1990470594 @default.
- W2611907400 cites W1993044982 @default.
- W2611907400 cites W1999642390 @default.
- W2611907400 cites W2003706451 @default.
- W2611907400 cites W2004428159 @default.
- W2611907400 cites W2004918900 @default.
- W2611907400 cites W2007817757 @default.
- W2611907400 cites W2014605936 @default.
- W2611907400 cites W2020471978 @default.
- W2611907400 cites W2026940625 @default.
- W2611907400 cites W2027828332 @default.
- W2611907400 cites W2028093592 @default.
- W2611907400 cites W2042497518 @default.
- W2611907400 cites W2044519583 @default.
- W2611907400 cites W204753584 @default.
- W2611907400 cites W2052899239 @default.
- W2611907400 cites W2056334970 @default.
- W2611907400 cites W2057850803 @default.
- W2611907400 cites W2058313010 @default.
- W2611907400 cites W2058411493 @default.
- W2611907400 cites W2062356494 @default.
- W2611907400 cites W2071905957 @default.
- W2611907400 cites W2082667898 @default.
- W2611907400 cites W2088226047 @default.
- W2611907400 cites W2088629793 @default.
- W2611907400 cites W2089475202 @default.
- W2611907400 cites W2094819196 @default.
- W2611907400 cites W2096093282 @default.
- W2611907400 cites W2097488520 @default.
- W2611907400 cites W2099450402 @default.
- W2611907400 cites W2100724457 @default.
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- W2611907400 cites W2107462101 @default.
- W2611907400 cites W2114839447 @default.
- W2611907400 cites W2122721018 @default.
- W2611907400 cites W2123749084 @default.
- W2611907400 cites W2130480188 @default.
- W2611907400 cites W2131887397 @default.
- W2611907400 cites W2137992445 @default.
- W2611907400 cites W2139811938 @default.
- W2611907400 cites W2139976486 @default.
- W2611907400 cites W2148233964 @default.
- W2611907400 cites W2149597323 @default.
- W2611907400 cites W2150502003 @default.
- W2611907400 cites W2154773472 @default.
- W2611907400 cites W2159983165 @default.
- W2611907400 cites W2179507357 @default.
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- W2611907400 cites W2951403306 @default.
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- W2611907400 doi "https://doi.org/10.1021/acs.jnatprod.6b00807" @default.
- W2611907400 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28463513" @default.
- W2611907400 hasPublicationYear "2017" @default.
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