Isolation and characterization of two genes encoding proteases associated with the mycelium of Streptomyces lividans 66

Binnie, Craig; Butler, Michael J.; Aphale, Jayant S.; Bourgault, Richard; DiZonno, M A; Krygsman, Phyllis; Liao, Linda M.; Walczyk, Eva; Malek, Lawrence T.

doi:10.1128/jb.177.21.6033-6040.1995

Cited by 18 publications

(17 citation statements)

References 16 publications

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“…Rv2224c is classified as an ␣/␤ hydrolase in a family with both esterase and amidase members (25). Its closest biochemically characterized homolog, the secreted SlpD triaminopeptidase from S. lividans, was identified by its activity against an amide (7). Protease activity is consistent with the requirement of Rv2224c for correct processing of GroEL2.…”

Section: Discussionmentioning

confidence: 73%

“…Rv2224c contains a GXSXG consensus sequence surrounding a putative serine active site (S 228 ), which is characteristic of ␣/␤ hydrolase-fold family members, namely proteases, esterases, and lipases. Rv2224c is annotated as a tripeptidyl peptidase in the MEROPS peptidase database, and its sequence shows high sequence similarity to the serine proteases SlpD and SlpE from Streptomyces lividans, which are mycelium-associated lipoproteins involved in cell growth (7). Refolded recombinant Rv2224c also has been reported to display esterase activity in vitro (8).…”

Section: Rv2224c Is Associated With the Mycobacterial Cell Envelopementioning

confidence: 99%

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Mycobacterium tuberculosis Rv2224c modulates innate immune responses

Rengarajan

Murphy

Park

et al. 2008

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

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Tuberculosis remains a major global health problem that kills up to 2 million people annually. Central to the success of Mycobacterium tuberculosis (Mtb) as a pathogen is its ability to evade host immunity and to establish a chronic infection. Although its primary intracellular niche is within macrophages, the underlying molecular mechanisms are poorly understood. Here we show that Rv2224c, a cell envelope-associated predicted protease, is critical for Mtb virulence. Disruption of Rv2224c led to prolonged survival of infected mice and highly reduced lung pathology. Absence of Rv2224c enhanced host innate immune responses, compromised the intracellular survival of Mtb in macrophages, and increased its susceptibility to lysozyme. We provide insights into the molecular basis for Rv2224c function by showing that Rv2224c activity promotes processing and extracellular release of the Mtb protein, GroEL2. Inhibition of Rv2224c and its targets offers opportunities for therapeutic interventions and immune-modulatory strategies.macrophages ͉ pathogen ͉ intracellular ͉ cell envelope

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Section: Discussionmentioning

confidence: 73%

Section: Rv2224c Is Associated With the Mycobacterial Cell Envelopementioning

confidence: 99%

Mycobacterium tuberculosis Rv2224c modulates innate immune responses

Rengarajan

Murphy

Park

et al. 2008

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

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“…This observation highlighted the difference in function(s) of the prx gene product and the S. lividans SlpE protease that is required for the effective growth of the strain on minimal media (Binnie et al, 1995). The mutant thus obtained grew and sporulated well on both complete and minimal media.…”

Section: Disruption Of Prx Affected Lae Production In Streptomyces Glmentioning

confidence: 84%

“…A 1 kb upstream section of lndI short non-overlapping DNA fragments had been found that showed homology to bacterial proteinases. Putative proteinases found in the Streptomyces coelicolor (genes SCO5180, SCO4241, SCO3540, SCO5179) and Streptomyces avermitillis (SAV3081, SAV3080) genomes (Bentley et al, 2002;Ikeda et al, 2003), as well as the previously studied Streptomyces lividans proteases SlpD and SlpE (Binnie et al, 1995) are the closest Prx homologues, with a similarity ranging from 55% to 72%. It was situated 700 bp upstream of lndI and had the same transcriptional direction (Fig.…”

Section: Resultsmentioning

confidence: 99%

A putative proteinase gene is involved in regulation of landomycin E biosynthesis inStreptomyces globisporus1912

Dutko

Rebets

Ostash

et al. 2006

FEMS Microbiology Letters

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The prx gene, which is highly homologous to putative proteinases, has been identified by sequencing in the vicinity of the biosynthetic gene cluster for landomycin E (LaE) biosynthesis (lnd) in Streptomyces globisporus 1912. The S. globisporus Pro6 gene, deficient in prx, produced fivefold less LaE than the parental strain. The expression of prx in S. globisporus Pro6 restored LaE production to wild-type levels, whereas expression of the pathway-specific regulatory gene lndI did not. The introduction of additional copies of prx into the wild-type strain using a pSG5-based plasmid, pKC1139, led to a 2.7-fold increase in LaE production. These results indicate that prx is a novel regulatory gene for LaE biosynthesis.

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“…It could even act on highly stable secreted proteins since depletion of this protease increased yield of extracellular a-amylase . In S. lividans, Binnie et al (1995) described two cell-associated proteinases, SlpD and SlpE. It is suggested that the function of these cell-associated proteases resembles that of E. coli DegP protease.…”

Section: )mentioning

confidence: 99%

Novel Frontiers in the Production of Compounds for Biomedical Use

Broekhoven¹,

Shapiro²,

Anne³

2002

Focus on Biotechnology

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COLOPHON Focus onBiotechnology is an open-ended series of reference volumes produced for Kluwer Academic Publishers BV in co-operation with the Branche Belge de la Société de Chimie Industrielle a.s.b.l.The initiative has been taken in conjunction with the Ninth European Congress on Biotechnology.The present book entitled "Novel Frontiers in the Production of Compounds for Biomedical Uses" can perhaps be placed in its best perspective by the Shakespearean character in The Tempest who exclaimed" What's past is prologue". Indeed, this compilation of some of the outstanding presentations in the field of biomedicine made at the 9 th European Congress on Biotechnology (Brussels, Belgium, July 11-15, 1999) not only reflects the achievements of the recent past, but provides a privileged glimpse of the biotechnology that is emerging in the first decade of the new Millennium.It is becoming increasingly apparent that biotechnology is offering biomedicine novel approaches and solutions to develop a sorely needed new generation of biopharmaceuticals. This is all the more necessary because in recent years, new diseases have emerged with extraordinary lethality in all corners of the globe, while age-related chronic illnesses have filled the gap wherever biomedicine has made successful inroads. The rise of antibiotic resistance also poses major threats to public health. Thus, as disease patterns evolve, the rational development of new drugs is becoming urgent, not only for the clinical outcome of patients, but also in optimising the allocation of scarce health care resources through the use of cost-effective productions methods. It is in response to all these challenges that biotechnology offers new strategies that go beyond the more traditional approaches.By the mid-1990's, the number of recombinant products approved annually for therapeutic use reached double digits. With the advent of the genomics revolution. coupled with proteomics, bioinformatics, high-throughput screening, and microelectronics, the number of potential bioproducts entering clinical trials will surely grow almost exponentially. The improved availability of structural and functional biochemical information, together with rational drug design, will also help fill the drug development pipeline. And it should certainly not be forgotten that the increasing demand for recombinant compounds necessitates improved production systems.In order to better focus on the challenges at hand, the Editors have striven to adopt an integrative approach by selecting contributions linking genomics with bacterial resistance, antibiotics with improved production strategies, optimised production approaches with chemical development programs, chemical modifications with new antibody derivatives and biomaterials, the relation between bioartificial organs and xenotransplantation, apoptosis and process biotechnology, etc. It should be readily apparent from these chapters that the development of truly novel compounds for biomedical use not only requires leading-edge science and technolog...

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Isolation and characterization of two genes encoding proteases associated with the mycelium of Streptomyces lividans 66

Cited by 18 publications

References 16 publications

Mycobacterium tuberculosis Rv2224c modulates innate immune responses

Mycobacterium tuberculosis Rv2224c modulates innate immune responses

A putative proteinase gene is involved in regulation of landomycin E biosynthesis inStreptomyces globisporus1912

Novel Frontiers in the Production of Compounds for Biomedical Use

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