A two component-type cytochrome P-450 monooxygenase system in a prokaryote that catalyzes hydroxylation of ML-236B to pravastatin, a tissue-selective inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase

Serizawa, Nobufusa; Matsuoka, Tatsuji

doi:10.1016/0005-2760(91)90052-j

Cited by 59 publications

(24 citation statements)

References 15 publications

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“…Crespi et al (11) also reported the presence of a ferredoxin-like domain at the N terminus of a protein otherwise dissimilar to any protein involved in P450 reactions. A twocomponent bacterial cytochrome P450 system was reported by Serizawa and Matsuoka (38), with the reductase component containing both FAD and FMN groups and no ferredoxin being required for activity. A gene, xplB, with homology to adrenodoxin reductase, is found 62 bp upstream of xplA.…”

Section: Discussionmentioning

confidence: 99%

Cloning, Sequencing, and Characterization of the Hexahydro-1,3,5-Trinitro-1,3,5-Triazine Degradation Gene Cluster from Rhodococcus rhodochrous

Seth-Smith

Rosser

Basran

et al. 2002

Appl Environ Microbiol

176

126

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Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) is a high explosive which presents an environmental hazard as a major land and groundwater contaminant. Rhodococcus rhodochrous strain 11Y was isolated from explosive contaminated land and is capable of degrading RDX when provided as the sole source of nitrogen for growth. Products of RDX degradation in resting-cell incubations were analyzed and found to include nitrite, formaldehyde, and formate. No ammonium was excreted into the medium, and no dead-end metabolites were observed. The gene responsible for the degradation of RDX in strain 11Y is a constitutively expressed cytochrome P450-like gene, xplA, which is found in a gene cluster with an adrenodoxin reductase homologue, xplB. The cytochrome P450 also has a flavodoxin domain at the N terminus. This study is the first to present a gene which has been identified as being responsible for RDX biodegradation. The mechanism of action of XplA on RDX is thought to involve initial denitration followed by spontaneous ring cleavage and mineralization.Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) is one of the most important and widely used military explosives. Due to its manufacture, decommissioning, and disposal it has become a serious pollutant at many sites, particularly across the United States and Germany, and its recalcitrance in the environment has led to its persistence in soil and groundwater. RDX is a potent convulsant due to its effects on the central nervous system and is also a class C, possible, carcinogen (7).For a long time it was thought that RDX biodegradation could occur only under anaerobic conditions (15, 26); however, aerobic degradation of RDX has been more recently demonstrated by bacterial consortia and pure strains. Coryneform bacteria (45), Stenotrophomonas maltophilia strain PB1 (4), and a rhodococcal strain (9) have been shown to utilize RDX as a sole source of nitrogen, generally degrading RDX at higher rates than anaerobic systems do.The first pathway for the aerobic degradation of RDX by a strain of Rhodococcus was proposed very recently (16) and involves denitration as the first step followed by spontaneous ring cleavage (Fig. 1). Positively identified products include nitrite (NO 2 Ϫ ), nitrous oxide (N 2 O), formaldehyde (HCHO), and carbon dioxide. A dead-end intermediate with the molecular formula C 2 H 5 N 3 O 3 was also found to accumulate, indicating that not all the components of RDX were mineralized. This paper reports the isolation and identification of a Rhodococcus rhodochrous strain which can degrade RDX as a nitrogen source and the first cloning and expression of a gene responsible for RDX degradation. This gene is constitutively expressed, and its product has homology to a cytochrome P450. MATERIALS AND METHODSReagents. RDX (Ͼ95% purity as determined by high-performance liquid chromatography HPLC) was kindly provided by the Defence Science and Technology Laboratory (Dstl), Fort Halstead. Other chemicals were of analytical grade and, unless otherwise stated, were obtained from ...

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Section: Discussionmentioning

confidence: 99%

Cloning, Sequencing, and Characterization of the Hexahydro-1,3,5-Trinitro-1,3,5-Triazine Degradation Gene Cluster from Rhodococcus rhodochrous

Seth-Smith

Rosser

Basran

et al. 2002

Appl Environ Microbiol

176

126

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“…38 Although simvastatin is usually made from lovastatin chemically in a multistep process, an enzymatic/bioconversion process using recombinant Escherichia coli has been developed. 39 Another statin, pravastatin (Pravacol) ($3.6 billion in sales per year), is made via different biotransformation processes from compactin by Streptomyces carbophilus 40 and Actinomadura sp. 41 Both simvastatin and pravastatin are synthetic variants of the naturally occurring lovastatin and compactin.…”

Section: Anti-rejection Drugs (Agents That Suppress the Immune System)mentioning

confidence: 99%

Production of valuable compounds by molds and yeasts

Demain

Martens

2016

J Antibiot

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where he has contributed in a major way to the reputation of this department for many years. He also served as an Adjunct Professor at the University of Geneva. Among Julian's areas of study and accomplishment are fungal toxins including α-sarcin, chemical synthesis of triterpenes, mode of action of streptomycin and other aminoglycoside antibiotics, biochemical mechanisms of antibiotic resistance in clinical isolates of bacteria harboring resistance plasmids, their origins and evolution, secondary metabolism of microorganisms, structure and function of bacterial ribosomes, antibiotic resistance mutations in yeast ribosomes, cloning of resistance genes from an antibiotic-producing microbe, gene cloning for industrial purposes, engineering of herbicide resistance in useful crops, bleomycin-resistance gene in clinical isolates of Staphylococcus aureus and many other topics. He has been an excellent teacher, lecturing in both English and French around the world, and has organized international courses. Julian has also served on the NIH study sections, as Editor for several international journals, and was one of the founders of the journal Plasmid. We expect the impact of Julian's accomplishments to continue into the future.

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“…A number of MCMOs play important roles as biocatalysts in commercially important biotechnological applications. This includes the hydroxylase from Streptomyces carbophilus SANK 62585 employed for the bioconversion of mevastatin into the widely used hypocholestemic drug pravastatin (Matsuoka et al 1989;Serizawa and Matsuoka 1991) and a number of luciferases exploited both directly and indirectly in various applications due to their characteristic bioluminescent properties (Hastings et al 1985;Meighen 1991).…”

Section: Introductionmentioning

confidence: 99%

Functional assembly of camphor converting two-component Baeyer–Villiger monooxygenases with a flavin reductase from E. coli

Kadow

Balke

Willetts³

et al. 2013

Appl Microbiol Biotechnol

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A two component-type cytochrome P-450 monooxygenase system in a prokaryote that catalyzes hydroxylation of ML-236B to pravastatin, a tissue-selective inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase

Cited by 59 publications

References 15 publications

Cloning, Sequencing, and Characterization of the Hexahydro-1,3,5-Trinitro-1,3,5-Triazine Degradation Gene Cluster from Rhodococcus rhodochrous

Cloning, Sequencing, and Characterization of the Hexahydro-1,3,5-Trinitro-1,3,5-Triazine Degradation Gene Cluster from Rhodococcus rhodochrous

Production of valuable compounds by molds and yeasts

Functional assembly of camphor converting two-component Baeyer–Villiger monooxygenases with a flavin reductase from E. coli

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