Patent classifications
C12Y305/01092
Use of VNN1 as a biomarker and a therapeutic target in sarcomas
Sarcomas are rare malignant tumors arising from the mesenchymal tissues at all body sites. The inventors show that in a mouse model of p16/p19 deficiency prone to tumor development, the absence of the mouse pantetheinase Vnn1 enhances the frequency of aggressive fibrosarcomas. They also show that reintroduction of a catalytically active form of the Vnn1 pantetheinase limits tumor growth in vivo. Interestingly, VNN1 expression in human sarcomas is associated with reduced aggressiveness and lower risk of metastatic relapse in patients. In conclusion, Vnn1 represents a novel marker of sarcoma and may modulate tumor aggressiveness by sustaining myofibroblast cell differentiation, thereby limiting evolution towards undifferentiated tumors. The present invention relates to the use of Vnn1 as a biomarker and a therapeutic target in sarcomas.
USE OF VNN1 AS A BIOMARKER AND A THERAPEUTIC TARGET IN SARCOMAS
Sarcomas are rare malignant tumors arising from the mesenchymal tissues at all body sites. The inventors show that in a mouse model of p16/p19 deficiency prone to tumor development, the absence of the mouse pantetheinase Vnn1 enhances the frequency of aggressive fibrosarcomas. They also show that reintroduction of a catalytically active form of the Vnn1 pantetheinase limits tumor growth in vivo. Interestingly, VNN1 expression in human sarcomas is associated with reduced aggressiveness and lower risk of metastatic relapse in patients. In conclusion, Vnn1 represents a novel marker of sarcoma and may modulate tumor aggressiveness by sustaining myofibroblast cell differentiation, thereby limiting evolution towards undifferentiated tumors. The present invention relates to the use of Vnn1 as a biomarker and a therapeutic target in sarcomas.
BIOSYNTHESIS OF SULFUR-CONTAINING COMPOUNDS USING GENETICALLY MODIFIED BACTERIA
A genetically modified prokaryotic cell which comprises: a cysteamine dioxygenase (ADO) polypeptide sequence which has at least 70% sequence coverage to SEQ 2, and at least 25% sequence identity to SEQ 2; and a vanin (VNN) polypeptide sequence selected from the group consisting of: a vanin-1 (VNN1) polypeptide sequence which has at least 70% sequence coverage to SEQ 4, and at least 25% sequence identity to SEQ 4; a vanin-2 (VNN2) polypeptide sequence which has at least 70% sequence coverage to SEQ 84, and at least 25% sequence identity to SEQ 84; and a vanin-3 (VNN3) polypeptide sequence which has at least 70% sequence coverage to SEQ 128 and at least 25% sequence identity to SEQ 128.
TAURINE BIOSYNTHESIS USING GENETICALLY MODIFIED BACTERIA
A genetically modified prokaryotic cell which comprises: a vanin (vnn) polynucleotide sequence selected from the group consisting of: vanin-1 (vnn1), wherein said vnn1 polynucleotide sequence has at least 70% sequence coverage to SEQ 3 or SEQ 98, and at least 70% sequence identity to SEQ 3 or SEQ 98; vanin-2 (vnn2), wherein said vnn2 polynucleotide sequence has at least 70% sequence coverage to SEQ 100, and at least 70% sequence identity to SEQ 100; and vanin-3 (vnn3), wherein said vnn3 polynucleotide sequence has at least 70% sequence coverage to SEQ 141, and at least 70% sequence identity to SEQ 141; or a cysteamine dioxygenase (ado) polynucleotide sequence which has at least 70% sequence coverage to SEQ 1, and at least 70% sequence identity to SEQ 1; and a flavin-containing monooxygenase 1 (fmol) polynucleotide sequence which has at least 70% sequence coverage to SEQ 5 or SEQ 99, and at least 70% of sequence identity to SEQ 5 or SEQ 99.
METHOD TO PRODUCE ORGANOSULFUR COMPOUNDS USING GENETICALLY MODIFIED MICROORGANISMS
A method of producing an organosulfur compound from a prokaryotic cell wherein said method comprises the steps of: a. providing a live prokaryotic cell capable of expressing at least one gene for the production of said organosulfur compound; b. exposing said live prokaryotic cell to a culture media with a pH of between 4 and 11 containing a carbon source and a sulfur source thereby creating an incubation mixture; c. incubating said live prokaryotic cell in said incubation mixture under aerobic or anaerobic conditions at a temperature ranging from 0 C. to 60 C. for a period of time sufficient for the expression of said at least one gene for the production of said organosulfur compound; d. recovering said organosulfur compound from the bacterial cells and/or spent media; and e. optionally, re-exposing said live prokaryotic cell to an unused media or spent media for the continuous production of said organosulfur compound of interest.
TAURINE BIOSYNTHESIS USING GENETICALLY MODIFIED BACTERIA
A genetically modified prokaryotic cell comprising: at least one of the following: i. an addition, deletion and/or alteration of at least one gene to promote to taurine production; and ii. an addition, deletion and/or alteration of at least one gene related to taurine cellular transportation; and at least one of the following polynucleotide sequences: i. a vanin (vnn) polynucleotide sequence selected from the group consisting of: vanin-1 (vnn1), wherein said vnn1 polynucleotide sequence has at least 70% sequence coverage to SEQ 3 or SEQ 98, and at least 70% sequence identity to SEQ 3 or SEQ 98; vanin-2 (vnn2), wherein said vnn2 polynucleotide sequence has at least 70% sequence coverage to SEQ 100, and at least 70% sequence identity to SEQ 100; and vanin-3 (vnn3), wherein said vnn3 polynucleotide sequence has at least 70% sequence coverage to SEQ 141, and at least 70% sequence identity to SEQ 141; ii. a cysteamine dioxygenase (ado) polynucleotide sequence which has at least 70% sequence coverage to SEQ 1, and at least 70% sequence identity to SEQ 1; and iii. a flavin-containing monooxygenase 1 (fmo1) polynucleotide sequence which has at least 70% sequence coverage to SEQ 5 or SEQ 99, and at least 70% of sequence identity to SEQ 5 or SEQ 99.