Cysteine biosynthesis in Saccharomyces cerevisiae : a new outlook on pathway and regulation

Ono, Bun‐Ichiro; Hazu, Toshiya; Yoshida, Sayaka; Kawato, Takahiro; Shinoda, Sumió; Brzvwczy, Jerzy; Paszewski, Andrzej

doi:10.1002/(sici)1097-0061(19990930)15:13<1365::aid-yea468>3.3.co;2-l

Cited by 26 publications

(57 citation statements)

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“…Influences of a possible sulfide acceptor on H 2 S production and respiratory oscillation Although the synthesis of O-acetylserine and the role of O-acetylhomoserine /O-acetylserine sulfhydrylase in S. cerevisiae are still controversial (Ono et al 1991(Ono et al , 1996(Ono et al , 1999Cherest and Surdin-Kerjan 1992;Cherest et al 1993), an O-modified sulfide acceptor is an essential precursor in the synthesis of sulfur amino acids as a carbon skeleton. Pulse injection of 100 µM of O-acetylhomoser- ine at a minimal dissolved O 2 concentrations increased H 2 S production 1.6-fold in the subsequent cycle and transiently perturbed respiratory oscillation (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…However, cysteine (or its derivative), rather than S-adenosylmethionine/methionine, has been continuously postulated as an essential regulator of sulfate assimilation (Ono et al 1991(Ono et al , 1999Hansen and Johannesen 2000) because O-acetylhomoserine/O-acetylserine sulfhydrylase is not inhibited by S-adenosylmethionine and methionine in mutants deficient in the reverse-transsulfuration pathway (Ono et al 1996).…”

Section: Ho-yong Sohn · Hiroshi Kuriyamamentioning

confidence: 99%

“…H 2 S, an end-product of the sulfate assimilation (SA) pathway, is incorporated into homocysteine by the γ-replacement reaction of O-acetylhomoserine, and homocysteine is further converted to various sulfur compounds ( Fig. 1) (Marzluf 1997;Ono et al 1999;Hansen and Johannesen 2000).…”

Section: Introductionmentioning

confidence: 99%

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The role of amino acids in the regulation of hydrogen sulfide production during ultradian respiratory oscillation of Saccharomyces cerevisiae

Sohn

Kuriyama

2001

Archives of Microbiology

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We previously demonstrated that periodic H2S production during aerobic continuous culture of Saccharomyces cerevisiae resulted in ultradian respiratory oscillation, and that H2S production was dependent on the activity of sulfate uptake and the level of sulfite. To investigate the mechanism of regulation of the sulfate assimilation pathway and of respiratory oscillation, several amino acids were pulse-injected into cultures during respiratory oscillation. Injection of sulfur amino acids or their derivatives perturbed respiratory oscillation, with changes in the H2S production profile. Four major regulators of H2S production in the sulfate assimilation pathway and respiratory oscillation were identified: (1) O-acetylhomoserine, not O-acetylserine, as a sulfide acceptor, (2) homoserine/threonine as a regulator of O-acetylhomoserine supply, (3) methionine/S-adenosyl methionine as a negative regulator of sulfate assimilation, and (4) cysteine (or its derivatives) as an essential regulator. The results obtained after the addition of DL-propargylglycine (5 microM and 100 microM) and cystathionine (50 microM) suggested that the intracellular cysteine level and cystathionine gamma-lyase, rather than methionine/S-adenosylmethionine, play an essential role in the regulation of sulfate assimilation and respiratory oscillation. Based on these results and those of our previous reports, we propose that periodic depletion of cysteine (or its derivatives), which is involved in the detoxification of toxic materials originating from respiration, causes periodic H2S production.

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Section: Resultsmentioning

confidence: 99%

Section: Ho-yong Sohn · Hiroshi Kuriyamamentioning

confidence: 99%

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The role of amino acids in the regulation of hydrogen sulfide production during ultradian respiratory oscillation of Saccharomyces cerevisiae

Sohn

Kuriyama

2001

Archives of Microbiology

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“…1-ii, b). In the budding yeast Saccharomyces cerevisiae, well studied in terms of sulphur metabolism, cysteine is predominantly synthesized via the cystathionine pathway 3) although activities of enzymes involved in OAS pathway are detected in some strains 4,5) (Fig. 1-i).…”

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confidence: 99%

Characterization of Two Genes Encoding Putative Cysteine Synthase Required for Cysteine Biosynthesis inSchizosaccharomyces pombe

Fujita

Takegawa

2004

Bioscience, Biotechnology, and Biochemistry

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“…This technique resulted in obtaining 5% gene disruption (one event in every 20 transformants); thus, the expected gene disruption efficiency (0.5%) was increased 10-fold. The use of this enrichment method in our laboratory has resulted in very high efficiencies (30% of gene disruption events) for the inactivation of In Saccharomyces cerevisiae and filamentous fungi, cysteine is synthesized by two pathways (25,26) (Fig. 1).…”

Section: Discussionmentioning

confidence: 99%

Targeted Inactivation of the mecB Gene, Encoding Cystathionine-γ-Lyase, Shows that the Reverse Transsulfuration Pathway Is Required for High-Level Cephalosporin Biosynthesis in Acremonium chrysogenum C10 but Not for Methionine Induction of the Cephalosporin Genes

et al. 2001

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Targeted gene disruption efficiency in Acremonium chrysogenum was increased 10-fold by applying the double-marker enrichment technique to this filamentous fungus. Disruption of the mecB gene by the doublemarker technique was achieved in 5% of the transformants screened. Mutants T6 and T24, obtained by gene replacement, showed an inactive mecB gene by Southern blot analysis and no cystathionine-␥-lyase activity. These mutants exhibited lower cephalosporin production than that of the control strain, A. chrysogenum C10, in MDFA medium supplemented with methionine. However, there was no difference in cephalosporin production between parental strain A. chrysogenum C10 and the mutants T6 and T24 in Shen's defined fermentation medium (MDFA) without methionine. These results indicate that the supply of cysteine through the transsulfuration pathway is required for high-level cephalosporin biosynthesis but not for low-level production of this antibiotic in methionine-unsupplemented medium. Therefore, cysteine for cephalosporin biosynthesis in A. chrysogenum derives from the autotrophic (SH 2 ) and the reverse transsulfuration pathways. Levels of methionine induction of the cephalosporin biosynthesis gene pcbC were identical in the parental strain and the mecB mutants, indicating that the induction effect is not mediated by cystathionine-␥-lyase. ␤-Lactam biosynthesis inAcremonium chrysogenum (formerly known as Cephalosporium acremonium) begins with the nonribosomal condensation of the three precursor amino acids L-␣-aminoadipic acid, L-cysteine, and L-valine (1, 21, 23). There are two ways to synthesize cysteine in filamentous fungi (35,26). One pathway, the so-called autotrophic pathway, converts inorganic sulfur to cysteine via serine O-acetyltransferase and O-acetylserine sulfhydrilase (Fig. 1). In the second route, cysteine can be obtained via the reverse transsulfuration pathway, in which the sulfur atom of methionine is transferred to cysteine through S-adenosylmethionine, S-adenosylhomocysteine, homocysteine, and cystathionine as intermediates.The predominant route of the cysteine supply for ␤-lactam biosynthesis depends on the producer microorganism (6). Cysteine for penicillin biosynthesis in Penicillium chrysogenum is obtained mainly from sulfate reduction (31). In this microorganism, the transsulfuration pathway has been considered to have a minor role in penicillin biosynthesis. On the other hand, the sulfur atom for ␤-lactam biosynthesis by A. chrysogenum is believed to derive preferentially from methionine via the reverse transsulfuration pathway (3, 24). However, there is no genetic evidence for, or against, this hypothesis.DL-Methionine is known to stimulate cephalosporin biosynthesis in A. chrysogenum (7, 16). For many years it was unclear whether the stimulatory effect of DL-methionine was due to a precursor effect (one providing cysteine) or to an inducing effect (8,20,23). Sawada and coworkers established that methionine increases isopenicillin N synthase, deacetoxycephalosporin C synthase (30), and ␣-...

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Cysteine biosynthesis in Saccharomyces cerevisiae : a new outlook on pathway and regulation

Cited by 26 publications

References 26 publications

The role of amino acids in the regulation of hydrogen sulfide production during ultradian respiratory oscillation of Saccharomyces cerevisiae

The role of amino acids in the regulation of hydrogen sulfide production during ultradian respiratory oscillation of Saccharomyces cerevisiae

Characterization of Two Genes Encoding Putative Cysteine Synthase Required for Cysteine Biosynthesis inSchizosaccharomyces pombe

Targeted Inactivation of the mecB Gene, Encoding Cystathionine-γ-Lyase, Shows that the Reverse Transsulfuration Pathway Is Required for High-Level Cephalosporin Biosynthesis in Acremonium chrysogenum C10 but Not for Methionine Induction of the Cephalosporin Genes

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