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4'-Deoxypyridoxine disrupts vitamin B6 homeostasis in Escherichia coli K12 through combined inhibition of cumulative B6 uptake and PLP-dependent enzyme activity

Journal Article · · Microbiology
DOI:https://doi.org/10.1099/mic.0.001319· OSTI ID:2470825
 [1];  [2];  [3];  [4];  [3];  [1]
  1. Univ. of Florida, Gainesville, FL (United States)
  2. Consiglio Nazionale delle Ricerche (CNR), Roma (Italy); Sapienza Università di Roma, Rome (Italy)
  3. Sapienza Università di Roma, Rome (Italy)
  4. Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
+ Show Author Affiliations
Pyridoxal 5'-phosphate (PLP) is the active form of vitamin B6and a cofactor for many essential metabolic processes such as amino acid biosynthesis and one carbon metabolism. 4’-deoxypyridoxine (4dPN) is a long known B6antimetabolite but its mechanism of action was not totally clear. By exploring different conditions in which PLP metabolism is affected in the model organism Escherichia coli K12, we showed that 4dPN cannot be used as a source of vitamin B6as previously claimed and that it is toxic in several conditions where vitamin B6homeostasis is affected, such as in a B6auxotroph or in a mutant lacking the recently discovered PLP homeostasis gene, yggS. In addition, we found that 4dPN sensitivity is likely the result of multiple modes of toxicity, including inhibition of PLP-dependent enzyme activity by 4’-deoxypyridoxine phosphate (4dPNP) and inhibition of cumulative pyridoxine (PN) uptake. These toxicities are largely dependent on the phosphorylation of 4dPN by pyridoxal kinase (PdxK).
Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
2470825
Journal Information:
Microbiology, Journal Name: Microbiology Journal Issue: 4 Vol. 169; ISSN 1350-0872
Publisher:
Microbiology SocietyCopyright Statement
Country of Publication:
United States
Language:
English

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Hidden resources in the Escherichia coli genome restore PLP synthesis and robust growth after deletion of the essential gene pdxB journal November 2019
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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Pyridoxal 5′-phosphate
anti-metabolite
competitive inhibition