Abstract:
:The molecular basis of the ability of bacteria to live on caffeine via the C-8 oxidation pathway is unknown. The first step of this pathway, caffeine to trimethyluric acid (TMU), has been attributed to poorly characterized caffeine oxidases and a novel quinone-dependent caffeine dehydrogenase. Here, we report the detailed characterization of the second enzyme, a novel NADH-dependent trimethyluric acid monooxygenase (TmuM), a flavoprotein that catalyzes the conversion of TMU to 1,3,7-trimethyl-5-hydroxyisourate (TM-HIU). This product spontaneously decomposes to racemic 3,6,8-trimethylallantoin (TMA). TmuM prefers trimethyluric acids and, to a lesser extent, dimethyluric acids as substrates, but it exhibits no activity on uric acid. Homology models of TmuM against uric acid oxidase HpxO (which catalyzes uric acid to 5-hydroxyisourate) reveal a much bigger and hydrophobic cavity to accommodate the larger substrates. Genes involved in the caffeine C-8 oxidation pathway are located in a 25.2-kb genomic DNA fragment of CBB1, including cdhABC (coding for caffeine dehydrogenase) and tmuM (coding for TmuM). Comparison of this gene cluster to the uric acid-metabolizing gene cluster and pathway of Klebsiella pneumoniae revealed two major open reading frames coding for the conversion of TM-HIU to S-(+)-trimethylallantoin [S-(+)-TMA]. The first one, designated tmuH, codes for a putative TM-HIU hydrolase, which catalyzes the conversion of TM-HIU to 3,6,8-trimethyl-2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline (TM-OHCU). The second one, designated tmuD, codes for a putative TM-OHCU decarboxylase which catalyzes the conversion of TM-OHCU to S-(+)-TMA. Based on a combination of enzymology and gene-analysis, a new degradative pathway for caffeine has been proposed via TMU, TM-HIU, TM-OHCU to S-(+)-TMA.
journal_name
J Bacterioljournal_title
Journal of bacteriologyauthors
Mohanty SK,Yu CL,Das S,Louie TM,Gakhar L,Subramanian Mdoi
10.1128/JB.00597-12subject
Has Abstractpub_date
2012-08-01 00:00:00pages
3872-82issue
15eissn
0021-9193issn
1098-5530pii
JB.00597-12journal_volume
194pub_type
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journal_title:Journal of bacteriology
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journal_title:Journal of bacteriology
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doi:10.1128/jb.172.8.4610-4615.1990
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更新日期:1994-10-01 00:00:00
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doi:10.1128/JB.135.3.1062-1069.1978
更新日期:1978-09-01 00:00:00
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journal_title:Journal of bacteriology
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pub_type: 杂志文章
doi:10.1128/JB.98.3.1342-1354.1969
更新日期:1969-06-01 00:00:00
abstract::Wallis, Craig (Baylor University College of Medicine, Houston, Tex.), Joseph L. Melnick, and Fred Rapp. Effects of pancreatin on the growth of reovirus. J. Bacteriol. 92:155-160. 1966.-The influence of pancreatin and other proteolytic enzymes on the growth, plaque formation, and antigenicity of reovirus was studied. S...
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pub_type: 杂志文章
doi:10.1128/JB.92.1.155-160.1966
更新日期:1966-07-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/JB.109.2.773-779.1972
更新日期:1972-02-01 00:00:00
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doi:10.1128/JB.88.4.1065-1070.1964
更新日期:1964-10-01 00:00:00
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journal_title:Journal of bacteriology
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pub_type: 杂志文章
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更新日期:1989-02-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/JB.105.1.396-407.1971
更新日期:1971-01-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/jb.172.12.6849-6855.1990
更新日期:1990-12-01 00:00:00
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pub_type: 杂志文章
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更新日期:2008-01-01 00:00:00
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pub_type: 杂志文章
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更新日期:2002-11-01 00:00:00
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journal_title:Journal of bacteriology
pub_type: 杂志文章
doi:10.1128/JB.94.3.691-699.1967
更新日期:1967-09-01 00:00:00