Studies on the Formation of Bacitracin by Bacillus licheniformis: Role of Catabolite Repression and Organic Acids

Haavik, H. I.

doi:10.1099/00221287-84-2-321

Cited by 41 publications

(19 citation statements)

References 3 publications

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“…Because other useful secondary metabolites are inhibited by glucose (6,11,20,26,45), it would be advantageous to engineer strains for which glucose could support both growth and generation of secondary metabolites. The basis for the glucose inhibition of the prodigiosin phenotype (GIP) is incompletely understood, but GIP has been observed in several studies (4,8,15,27).…”

mentioning

confidence: 99%

Serratia marcescens Quinoprotein Glucose Dehydrogenase Activity Mediates Medium Acidification and Inhibition of Prodigiosin Production by Glucose

Fender

Bender

Stella

et al. 2012

Appl Environ Microbiol

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ABSTRACTSerratia marcescensis a model organism for the study of secondary metabolites. The biologically active pigment prodigiosin (2-methyl-3-pentyl-6-methoxyprodiginine), like many other secondary metabolites, is inhibited by growth in glucose-rich medium. Whereas previous studies indicated that this inhibitory effect was pH dependent and did not require cyclic AMP (cAMP), there is no information on the genes involved in mediating this phenomenon. Here we used transposon mutagenesis to identify genes involved in the inhibition of prodigiosin by glucose. Multiple genetic loci involved in quinoprotein glucose dehydrogenase (GDH) activity were found to be required for glucose inhibition of prodigiosin production, including pyrroloquinoline quinone and ubiquinone biosynthetic genes. Upon assessing whether the enzymatic products of GDH activity were involved in the inhibitory effect, we observed thatd-glucono-1,5-lactone andd-gluconic acid, but notd-gluconate, were able to inhibit prodigiosin production. These data support a model in which the oxidation ofd-glucose by quinoprotein GDH initiates a reduction in pH that inhibits prodigiosin production through transcriptional control of the prodigiosin biosynthetic operon, providing new insight into the genetic pathways that control prodigiosin production. Strains generated in this report may be useful in large-scale production of secondary metabolites.

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confidence: 99%

Serratia marcescens Quinoprotein Glucose Dehydrogenase Activity Mediates Medium Acidification and Inhibition of Prodigiosin Production by Glucose

Fender

Bender

Stella

et al. 2012

Appl Environ Microbiol

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“…showed a similar inhibitory effect (to 19% of maximal control specific activity), whereas 10 ,uM acridine orange did not significantly change the level of enzyme induction (85% of control).…”

Section: Resultsmentioning

confidence: 76%

“…Complete repression by-glucose of puromycin production on agar was found in buffered HT agar over the pH range 6.0 to 7.5 and therefore was not simply caused by organic acid production and a lowering ofpH (10). Also, in all ofthe liquid studies, CaCO3 was added to cells growing in CSL-CS and HT containing 1% glucose and was found to maintain the pH above 7.…”

Section: Resultsmentioning

confidence: 99%

Biosynthesis of Puromycin in Streptomyces alboniger : Regulation and Properties of O -Demethylpuromycin O -Methyltransferase

Sankaran

Pogell

1975

Antimicrob Agents Chemother

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Mechanisms for regulation of puromycin biosynthesis in Streptomyces alboniger were studied by measuring the levels of S-adenosyl-L-methionine:O-demethylpuromycin O-methyltransferase. The enzyme was released in soluble form from mycelia by 3 to 5 min of sonication at 4 C. Maximal specific activities of 0.7 and 0.1 nmollmin per mg of protein were found in cells grown in corn steep liquor-corn starch and Hickey-Tresner media, respectively. In both media, the O-methyltransferase activity rose from low levels to a maximum during midlogarithmic growth and then declined or disappeared completely (in HickeyTresner medium) during stationary phase. Either glucose (1%) or ethidium bromide (5 ,uM) reduced O-methyltransferase formation to very low levels with no effect on overall growth. Complete glucose repression of antibiotic formation occurred on agar. Cells grown in the presence of ethidium bromide continued to produce low enzyme levels after regrowth in the absence of dye, but formed normal amounts of puromycin on Hickey-Tresner agar. The O-methyltransferase, either crude or purified, was rapidly inactivated at 37 C. Each substrate alone, or both together at lower concentrations, protected against this loss of activity. Puromycin inhibited the transferase. Regulation of O-methyltransferase synthesis in S. alboniger includes (i) induction early in growth that is susceptible to catabolite repression and differential inhibition by ethidium bromide, and (ii) protection of the enzyme from inactivation by increased intracellular levels of its substrates. The O-methyltransferase was purified 30-to 40-fold by a combination of protamine sulfate precipitation, ammonium sulfate fractionation, adsorption and gradient salt elution from diethylaminoethylcellulose and Sephadex G-200 gel filtration. The enzyme was very unstable, even at low temperatures, upon purification beyond the salt fractionation step, but was stabilized by the addition of S-adenosyl-L-methionine during later stages of purification.Streptomyces alboniger produces puromycin, an antitumor agent and protein synthesis inhibitor (29). A specific enzyme which catalyzes the transfer of methyl groups from S-adenosyl-Lmethionine (SAM) to O-demethylpuromycin (ODMP) has been found in soluble extracts ofS. alboniger (26) (SAM:ODMP O-methyltransferase). This reaction is presumed to be the terminal biosynthetic step in the formation of the antibiotic. ODMP has been synthesized chemically (26) and is also found in trace quantities, together with the other demethyl derivatives, in commerical. puromycin samples (23).We have followed the activity of the O-methyltransferase as a marker during the growth cycle of the organism under varied cultivation conditions to ascertain the regulatory mechanisms involved in puromycin biosynthesis. The peculiar time sequence ofappearance and disap-

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“…This was different from bacitracin production. 6 ) That is, in the case of bacitracin, the addition of pyruvate at a neutral pH did not prevent the antibiotic production, while in this case, the supplementation with pyruvate suppressed NVG production in neutral conditions.…”

Section: Discussionmentioning

confidence: 99%

Carbon Catabolite Regulation of Neoviridogrisein Production by Glucose

Nagato¹,

Okumura²,

Okamoto³

et al. 1984

Agricultural and Biological Chemistry

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Studies on the Formation of Bacitracin by Bacillus licheniformis: Role of Catabolite Repression and Organic Acids

Cited by 41 publications

References 3 publications

Serratia marcescens Quinoprotein Glucose Dehydrogenase Activity Mediates Medium Acidification and Inhibition of Prodigiosin Production by Glucose

Serratia marcescens Quinoprotein Glucose Dehydrogenase Activity Mediates Medium Acidification and Inhibition of Prodigiosin Production by Glucose

Biosynthesis of Puromycin in Streptomyces alboniger : Regulation and Properties of O -Demethylpuromycin O -Methyltransferase

Carbon Catabolite Regulation of Neoviridogrisein Production by Glucose

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