Abstract:
:The biosynthetic gene cluster of lankamycin (LM), a 14-member macrolide antibiotic, is encoded on the 210-kb linear plasmid pSLA2-L in Streptomyces rochei 7434AN4. LM contains a 3-hydroxy-2-butyl group at the C-13 position, which is different from an ethyl group in erythromycin. The following two possibilities could be considered for the origin of this starter moiety of LM biosynthesis: (i) an extra module exists in the biosynthetic gene cluster and loads an additional acetate molecule, or (ii) 3-hydroxy-2-butyrate or its equivalent is loaded and incorporated as a starter. The former possibility was eliminated by the complete sequencing of pSLA2-L, which showed no extra module. On the other hand, the latter was confirmed by incorporation of deuterium in [3-(2)H]dl-isoleucine into the C-14 position of LM. The timing of hydroxylation reactions at the C-15 and C-8 positions of LM was studied by constructing disruptants of two P450 hydroxylase genes, lkmF (orf26) and lkmK (orf37). The lkmF disruptant produced 8-deoxylankamycin, while the lkmK disruptant produced both 15-deoxylankamycin and 8,15-dideoxylankamycin. These results clearly showed that LkmF is a C-8 hydroxylase and LkmK is a C-15 hydroxylase in LM biosynthesis and in addition suggested the order of hydroxylation steps; namely, hydroxylation may occur at first at C-15 by LkmK and then at C-8 by LkmF.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Arakawa K,Kodama K,Tatsuno S,Ide S,Kinashi Hdoi
10.1128/AAC.00016-06subject
Has Abstractpub_date
2006-06-01 00:00:00pages
1946-52issue
6eissn
0066-4804issn
1098-6596pii
50/6/1946journal_volume
50pub_type
杂志文章abstract::During a 4-month period in late 1988, we isolated ceftazidime-resistant strains of Klebsiella pneumoniae and other members of the family Enterobacteriaceae from 29 patients at a chronic-care facility in Massachusetts. Ceftazidime resistance resulted from two distinct extended-spectrum beta-lactamases of the TEM type w...
journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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doi:10.1128/aac.37.6.1305
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.37.11.2438
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pub_type: 杂志文章
doi:10.1128/aac.18.6.944
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.2.419
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abstract::The class C beta-lactamase of Citrobacter freundii GN346 is a typical cephalosporinase comprising 361 amino acids, and substitution of the glutamic acid at position 219 in the enzyme by lysine was previously shown to broaden its substrate spectrum to oxyimino beta-lactams (K. Tsukamoto, R. Ohno, and T. Sawai, J. Bacte...
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pub_type: 杂志文章
doi:10.1128/aac.38.6.1374
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,多中心研究
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更新日期:2015-07-01 00:00:00
abstract::TEM-28 (pI 6.1), expressed by an Escherichia coli clinical isolate, is a novel beta-lactamase which hydrolyzed ceftazidime, cefotaxime, and aztreonam with rates of 25, 1.1, and 5.6, respectively, relative to that for benzylpenicillin (100). The nucleotide sequence of blaTEM-28 differed from that of blaTEM-1 by two bas...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.40.1.260
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abstract::Echinocandins are recommended as the first-line drugs for the treatment of systemic candidiasis. Cas5 is a key transcription factor involved in the response to cell wall damage induced by echinocandins. In this study, through a genetic screen, we identified a second transcription factor, Efg1, that is also crucial for...
journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2016-09-23 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
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更新日期:1999-05-01 00:00:00