Intermediary Metabolism and Antibiotic Synthesis

Bu’Lock, J. D.

doi:10.1016/s0065-2164(08)70514-8

Cited by 185 publications

(66 citation statements)

References 64 publications

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“…Secondary metabolism is commonly associated with sporulation processes in microorganisms (56,77,113), including fungi (21,103). Secondary metabolites associated with sporulation can be placed into three broad categories: (i) metabolites that activate sporulation (for example, the linoleic acidderived compounds produced by A. nidulans [23,26,27,79]), (ii) pigments required for sporulation structures (for example melanins required for the formation or integrity of both sexual and asexual spores and overwintering bodies [6,63]), and (iii) toxic metabolites secreted by growing colonies at the approximate time of sporulation (for example the biosynthesis of some deleterious natural products, such as mycotoxins [55,120]).…”

Section: Secondary Metabolism Is Associated With Developmental Processesmentioning

confidence: 99%

“…Secondary metabolite production usually commences late in the growth of the microbe, often upon entering the stationary or resting phase (21). In early observations it was noted that the environmental conditions required for sporulation and secondary metabolism were often similar and were more stringent than those for pure vegetative growth (21,51,103).…”

Section: Secondary Metabolites That Are Sporogenic Factorsmentioning

confidence: 99%

“…In early observations it was noted that the environmental conditions required for sporulation and secondary metabolism were often similar and were more stringent than those for pure vegetative growth (21,51,103). Although it was once thought that natural products were essential for sporulation, there are many examples of fungal strains that still sporulate but are deficient in secondary metabolite production, for example, Penicillium urticae patulin mutants (103) and A. nidulans sterigmatocystin mutants (106).…”

Section: Secondary Metabolites That Are Sporogenic Factorsmentioning

confidence: 99%

“…In this review we will use the terms interchangeably. In many cases, the benefit these compounds confer on the organism is unknown (21). However, interest in these compounds is considerable, as many natural products are of medical, industrial and/or agricultural importance.…”

Section: Introductionmentioning

confidence: 99%

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Relationship between Secondary Metabolism and Fungal Development

Calvo

Wilson

Bok

et al. 2002

Microbiol Mol Biol Rev

944

652

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Filamentous fungi are unique organisms—rivaled only by actinomycetes and plants—in producing a wide range of natural products called secondary metabolites. These compounds are very diverse in structure and perform functions that are not always known. However, most secondary metabolites are produced after the fungus has completed its initial growth phase and is beginning a stage of development represented by the formation of spores. In this review, we describe secondary metabolites produced by fungi that act as sporogenic factors to influence fungal development, are required for spore viability, or are produced at a time in the life cycle that coincides with development. We describe environmental and genetic factors that can influence the production of secondary metabolites. In the case of the filamentous fungus Aspergillus nidulans, we review the only described work that genetically links the sporulation of this fungus to the production of the mycotoxin sterigmatocystin through a shared G-protein signaling pathway

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Section: Secondary Metabolism Is Associated With Developmental Processesmentioning

confidence: 99%

Section: Secondary Metabolites That Are Sporogenic Factorsmentioning

confidence: 99%

Section: Secondary Metabolites That Are Sporogenic Factorsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Relationship between Secondary Metabolism and Fungal Development

Calvo

Wilson

Bok

et al. 2002

Microbiol Mol Biol Rev

944

652

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“…Prodigiosin has been traditionally known as a secondary metabolite: it has no clearly defined function in cellular metabolism (4). Several physiological processes in S. marcescens, including prodigiosin pigmentation and biofilm formation, are activated at high cell density by quorum-sensing mechanisms (26,28,30).…”

mentioning

confidence: 99%

Kinetic Analysis of Growth Rate, ATP, and Pigmentation Suggests an Energy-Spilling Function for the Pigment Prodigiosin ofSerratia marcescens

Haddix¹,

Jones²,

Patel³

et al. 2008

J Bacteriol

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Serratia marcescens is a gram-negative environmental bacterium and opportunistic pathogen. S. marcescens expresses prodigiosin, a bright red and cell-associated pigment which has no known biological function for producing cells. We present here a kinetic model relating cell, ATP, and prodigiosin concentration changes for S. marcescens during cultivation in batch culture. Cells were grown in a variety of complex broth media at temperatures which either promoted or essentially prevented pigmentation. High growth rates were accompanied by large decreases in cellular prodigiosin concentration; low growth rates were associated with rapid pigmentation. Prodigiosin was induced most strongly during limited growth as the population transitioned to stationary phase, suggesting a negative effect of this pigment on biomass production. Mathematically, the combined rate of formation of biomass and bioenergy (as ATP) was shown to be equivalent to the rate of prodigiosin production. Studies with cyanide inhibition of both oxidative phosphorylation and pigment production indicated that rates of biomass and net ATP synthesis were actually higher in the presence of cyanide, further suggesting a negative regulatory role for prodigiosin in cell and energy production under aerobic growth conditions. Considered in the context of the literature, these results suggest that prodigiosin reduces ATP production by a process termed energy spilling. This process may protect the cell by limiting production of reactive oxygen compounds. Other possible functions for prodigiosin as a mediator of cell death at population stationary phase are discussed.Serratia marcescens is a ubiquitous environmental bacterium which has been isolated from soil, water, and insects (6). This organism has emerged as an important nosocomial pathogen associated with respiratory infections, urinary tract infections, sepsis, wound infections, and conjunctivitis among wearers of contact lenses (13,19,27). Environmental isolates of S. marcescens express the red, cell-associated pigment prodigiosin, but identification of most clinical isolates must rely on other biochemical markers because the majority are not pigmented (13,27).Prodigiosin has been traditionally known as a secondary metabolite: it has no clearly defined function in cellular metabolism (4). Several physiological processes in S. marcescens, including prodigiosin pigmentation and biofilm formation, are activated at high cell density by quorum-sensing mechanisms (26,28,30). Low phosphate concentrations and temperatures below 37°C favor strong pigmentation (29). At least 12 pigmentation (pig) genes (A through J; M and N), arranged as part of a larger pig operon, encode enzymes for prodigiosin biosynthesis. In addition, a suite of regulatory proteins provides fine genetic control at the level of transcription. Quorum-sensing regulation of pig operon expression is mediated by SmaR and SmaI (secondary metabolite activator) (24, 25). SmaR is a repressor with DNA binding activity (8); transcriptional repression is mi...

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Kinetics of biosynthesis of polyene macrolide antibiotics in batch cultures: Cell maturation time

Martı́n

McDaniel

1975

Biotech & Bioengineering

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SummaryThe changes in several parameters of the candicidin fermentation (total, mycelium-associated, and extracellular product formation ; growth rate; DNA content; glucose utilization; dissolved oxygen in the broth; and oxygen uptake rate) during the trophophase-idiophase transition are compared with previously reported data for the polyene macrolides, candidin and candihexin. The maturation time, t,, and the product formation rate constant, k,, have been calculated for each of the three polyene macrolides using a simple mathematical model. Slow-feeding of glucose, which resulted in candidin and candihexin overproduction has been shown to increase the polyene formation rate constant and to retard trophophase to idiophase transition (longer maturation time). The opposite effect is achieved by repeated feeding of soybean meal. The values of the maturation times and polyene formation rates obtained were used to predict the production of polyene macrolide antibiotics in batch cultures.

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Intermediary Metabolism and Antibiotic Synthesis

Cited by 185 publications

References 64 publications

Relationship between Secondary Metabolism and Fungal Development

Relationship between Secondary Metabolism and Fungal Development

Kinetic Analysis of Growth Rate, ATP, and Pigmentation Suggests an Energy-Spilling Function for the Pigment Prodigiosin ofSerratia marcescens

Kinetics of biosynthesis of polyene macrolide antibiotics in batch cultures: Cell maturation time

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