Bacterial heme biosynthesis and its biotechnological application

Frankenberg, Nicole; Moser, Jürgen; Jahn, Dieter

doi:10.1007/s00253-003-1432-2

Cited by 94 publications

(81 citation statements)

References 82 publications

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“…First, the large scale selective generation of relatively stable water soluble S-glutathionylated protoporphyrinogens in bacteria is of potential application in the delivery of porphyrin precursors for use as photodynamic dyes (30). For example, glutathionylated porphyrin derivatives would be actively transported by the ATP binding cassette transporter proteins overexpressed in drug-resistant tumors (43).…”

Section: Discussionmentioning

confidence: 99%

Binding and Glutathione Conjugation of Porphyrinogens by Plant Glutathione Transferases

Dixon

Lapthorn

Madesis

et al. 2008

Journal of Biological Chemistry

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Overexpression in Escherichia coli of a tau (U) class glutathione transferase (GST) from maize (Zea mays L.), termed ZmGSTU1, caused a reduction in heme levels and an accumulation of porphyrin precursors. This disruption was highly specific, with the expression of the closely related ZmGSTU2 or other maize GSTs having little effect. Expression in E. coli of a series of chimeric ZmGSTU1/ZmGSTU2 proteins identified domains responsible for disrupting porphyrin metabolism. In addition to known heme precursors, expression of ZmGSTU1 led to the accumulation of a novel glutathione conjugate of harderoporphyrin(ogen) (2,7,12,18-tetramethyl-3-vinylporphyrin-8,13,17-tripropionic acid). Using the related protoporphyrinogen as a substrate, conjugation could be shown to occur on one vinyl group and was actively catalyzed by the ZmGSTU. In plant transgenesis studies, the ZmGSTUs did not perturb porphyrin metabolism when expressed in the cytosol of Arabidopsis or tobacco. However, expression of a ZmGSTU1-ZmGSTU2 chimera in the chloroplasts of tobacco resulted in the accumulation of the harderoporphyrin(ogen)-glutathione conjugate observed in the expression studies in bacteria. Our results show that the well known ability of GSTs to act as ligand binding (ligandin) proteins of porphyrins in vitro results in highly specific interactions with porphyrinogen intermediates, which can be demonstrated in both plants and bacteria in vivo.

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Section: Discussionmentioning

confidence: 99%

Binding and Glutathione Conjugation of Porphyrinogens by Plant Glutathione Transferases

Dixon

Lapthorn

Madesis

et al. 2008

Journal of Biological Chemistry

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“…Heme feeds into the synthesis of both cytochromes and chlorophyll and thus plays a key role in enzymatic reactions, energy production, No Function Assignment -Singleton ORF has no neighborhood in the correct orientation above the score threshold or is adjacent to an ORF that cannot be characterized by similarity and metabolic regulation (38). In addition, it functions as a prosthetic group to proteins involved in bacterial stress response, oxidative damage, and virulence (39). Sequence analysis of the uncharacterized family reveals that it comprises hydrophobic, putative membrane-associated proteins that are unlikely to have enzymatic functions.…”

Section: Consistent Functional Characterization Of Orfs In Four Envirmentioning

confidence: 99%

Quantitative assessment of protein function prediction from metagenomics shotgun sequences

Harrington

Singh

Doerks

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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To assess the potential of protein function prediction in environmental genomics data, we analyzed shotgun sequences from four diverse and complex habitats. Using homology searches as well as customized gene neighborhood methods that incorporate intergenic and evolutionary distances, we inferred specific functions for 76% of the 1.4 million predicted ORFs in these samples (83% when nonspecific functions are considered). Surprisingly, these fractions are only slightly smaller than the corresponding ones in completely sequenced genomes (83% and 86%, respectively, by using the same methodology) and considerably higher than previously thought. For as many as 75,448 ORFs (5% of the total), only neighborhood methods can assign functions, illustrated here by a previously undescribed gene associated with the well characterized heme biosynthesis operon and a potential transcription factor that might regulate a coupling between fatty acid biosynthesis and degradation. Our results further suggest that, although functions can be inferred for most proteins on earth, many functions remain to be discovered in numerous small, rare protein families.fatty acid ͉ heme ͉ neighborhood ͉ environmental genomics ͉ metagenome annotation

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“…Heme has long been known to be required for respiration, oxygen metabolism, and electron transfer as the prosthetic group of hemoglobins, hydroxylases, catalases, peroxidases, and cytochromes. Moreover, heme acts as a regulatory molecule that controls cellular processes at the level of DNA transcription, RNA translation, protein stability and targeting, and cell differentiation (1,2).…”

Section: Paolo Ascenzimentioning

confidence: 99%