Two functional FAS-I type fatty acid synthases in Corynebacterium glutamicum

Radmacher, Eva; Alderwick, Luke J.; Besra, Gurdyal S.; Brown, Alistair K.; Gibson, Kevin J.; Sahm, Hermann; Eggeling, Lothar

doi:10.1099/mic.0.28012-0

Cited by 76 publications

(83 citation statements)

References 24 publications

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“…Unlike mycobacteria, which possess two fatty acid synthase systems (Fas-I and Fas-II), C. glutamicum has two Fas-I proteins (Fas-IA and Fas-IB) but lacks the Fas-II system. Fas-IA is essential for growth, whereas Fas-IB is not (18). The effect on fatty acid biosynthesis of disrupting acpS in C. glutamicum demonstrates that the Fas-IA enzyme is inactive in the ⌬acpS mutant, strongly suggesting that AcpS is responsible for the 4Ј-phosphopantetheinylation of this enzyme.…”

Section: The Acps and Pptt Pptases Are Involved In Fatty Acid And Mycmentioning

confidence: 89%

“…7, which is published as supporting information on the PNAS web site), indicating that the mutant was able to condense two C 18:1 fatty acids originated from the exogenous oleic acid. The absence of C 32 and C 34 corynomycolates from the cell envelope probably resulted from the large amounts of oleate in the growth medium (18). Unlike mycobacteria, which possess two fatty acid synthase systems (Fas-I and Fas-II), C. glutamicum has two Fas-I proteins (Fas-IA and Fas-IB) but lacks the Fas-II system.…”

Section: The Acps and Pptt Pptases Are Involved In Fatty Acid And Mycmentioning

confidence: 99%

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The nonredundant roles of two 4′-phosphopantetheinyl transferases in vital processes of Mycobacteria

Chalut

Botella

Silva

et al. 2006

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

124

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Mycobacterium tuberculosis contains >20 enzymes that require activation by transfer of the 4 -phosphopantetheine moiety of CoA onto a conserved serine residue, a posttranslational modification catalyzed by 4 -phosphopantetheinyl transferases (PPTases). The modified proteins are involved in key metabolic processes such as cell envelope biogenesis and the production of virulence factors. We show that two PPTases conserved in all Mycobacterium spp. and in related genera activate two different subsets of proteins and are not functionally redundant. One enzyme, AcpS, activates the two fatty acid synthase systems of mycobacteria, whereas the other PPTase, PptT, acts on type-I polyketide synthases and nonribosomal peptide synthases, both of which are involved in the biosynthesis of virulence factors. We demonstrate that both PPTases are essential for Mycobacterium smegmatis viability and that PptT is required for the survival of Mycobacterium bovis bacillus Calmette-Gué rin. These enzymes are thus central to the biology of mycobacteria and for mycobacterial pathogenesis and represent promising targets for new antituberculosis drugs.fatty acid synthase ͉ lipid metabolism ͉ mycolic acids ͉ polyketide

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Section: The Acps and Pptt Pptases Are Involved In Fatty Acid And Mycmentioning

confidence: 89%

Section: The Acps and Pptt Pptases Are Involved In Fatty Acid And Mycmentioning

confidence: 99%

The nonredundant roles of two 4′-phosphopantetheinyl transferases in vital processes of Mycobacteria

Chalut

Botella

Silva

et al. 2006

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

124

View full text Add to dashboard Cite

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“…Indeed, all the genes encoding the key enzymes of mycolic acid biosynthesis were identified: components of the type II-fatty acid synthase dissociated system (FAS-II), the mycolic acid condensing enzyme Pks13 and mycoloyltransferases (Table 3). In the A. subflavus genome, only one copy of fas (AS9A_3620), the gene encoding the multifunctional type I-FAS (FAS-I), was present, as is the case in M. tuberculosis (Cole et al, 1998) and N. farcinica (Ishikawa et al, 2004), and in contrast with C. glutamicum that has two fas copies (Ishikawa et al, 2004;Radmacher et al, 2005). The putative orthologues of the genes encoding the four catalytic steps of FAS-II (Marrakchi et al, 2008) were also present: the b-ketoacyl-ACP synthase fabF/kasA (AS9A_1223), the b-ketoacyl-ACP reductase fabG1/mabA (AS9A_1921), the b-hydroxyacyl-ACP dehydratase hadB (AS9A_0396) and the enoyl-ACP reductase inhA (AS9A_1922) ( Table 4).…”

Section: Genome Sequence Analysis In Light Of the Structural Datamentioning

confidence: 99%

A novel mycolic acid species defines two novel genera of the Actinobacteria, Hoyosella and Amycolicicoccus

et al. 2012

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A novel mycolic acid species defines two novel genera of the Actinobacteria, Hoyosella and Amycolicicoccus Corynebacterineae are characterized by the presence of long-chain lipids, notably mycolic acids (a-alkyl, b-hydroxy fatty acids), the structures of which are genus-specific. Mycolic acids from two environmental strains, Amycolicicoccus subflavus and Hoyosella altamirensis, were isolated and their structures were established using a combination of mass spectrometry analysis, 1 H-NMR spectroscopy and chemical degradations. The C 2 -C 3 cleavage of these C 30 -C 36 acids led to the formation of two fragments: saturated C 9 -C 11 acids, and saturated and unsaturated C 20 -C 25 aldehydes. Surprisingly, the fatty acids at the origin of the two fragments making up these mycolic acids were present in only minute amounts in the fatty acid pool. Moreover, the double bond in the main C 24 aldehyde fragment was located at position v16, whereas that found in the ethylenic fatty acids of the bacteria was at v9. These data question the biosynthesis of these new mycolic acids in terms of the nature of the precursors, chain elongation and desaturation. Nevertheless, they are consistent with the occurrence of the key genes of mycolic acid biosynthesis, including those encoding proteins of the fatty acid synthase II system, identified in the genome of A. subflavus. Altogether, while the presence of mycolic acids and analysis of their 16S rDNA sequences would suggest that these strains belong to the Mycobacteriaceae family, the originality of their structures reinforces the recent description of the novel genera Amycolicicoccus and Hoyosella. INTRODUCTIONThe suborder Corynebacterineae forms a large group of actinomycete species characterized by the presence of specific lipids, notably mycolic acids (a-alkyl, b-hydroxy long-chain fatty acids). The variability of their chain lengths and the complexity of their structures contribute to the definition of the genera, from the simplest corynomycolic acids of Corynebacterium to the most complex and species-specific mycolic acids of Mycobacterium, with intermediate chain-lengths in Rhodococcus, Nocardia and Gordonia (Barry et al., 1998). Recently two coccoidal strains have been isolated from environmental sources, Hoyosella altamirensis, from the Altamira cave in Spain, and Amycolicicoccus subflavus, from saline soil contaminated with crude oil in the Daqing Oilfield of eastern China (Jurado et al., 2009;Wang et al., 2010). By a polyphasic approach, the taxonomic position of the two species has been determined, i.e. Actinomycetales cell wall chemotype IV, menaquinones MK-8, diagnostic phosphatidylethanolamine and tuberculostearic acid. On the basis of 16S rRNA gene sequence analysis, the two species were shown to be most closely related to the genus Mycobacterium (95.6 % similarity with the Mycobacterium fallax type strain for Hoyosella, and 92.7-94.9 % similarity with Mycobacterium spp. for Amycolicicoccus). The two species differ from each other by their DNA G+C content, which is 49...

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“…tuberculosis, C. glutamicum encodes two fas genes (fasA and fasB) with FasA taking the dominant role [67]. The presence of two Fas proteins may compensate for the lack of a FAS-II system in this organism.…”

Section: De Novo Synthesis By Fas-imentioning

confidence: 99%