Molecule Information

General Information of the Molecule (ID: Mol01096)

• Name: Streptothricin acetyltransferase (STA) ,Streptomyces lavendulae
• Synonyms: STAT
• Molecule Type: Protein
• Gene Name: sta
• Sequence:
  MTTTHGSTYEFRSARPGDAEAIEGLDGSFTTSTVFEVDVTGDGFALREVPADPPLVKVFP
  DDGGSDGEDGAEGEDADSRTFVAVGADGDLAGFAAVSYSAWNQRLTIEDIEVAPGHRGKG
  IGRVLMRHAADFARERGAGHLWLEVTNVNAPAIHAYRRMGFAFCGLDSALYQGTASEGEH
  ALYMSMPCP
• Function: Involved in resistance to streptothricin, a broad-spectrum antibiotic produced by streptomycetes. Detoxifies streptothricin via acetylation of the beta amino group of the first beta-lysyl moiety of streptothricin.
• Uniprot ID: STA_STRLA

Kingdom: N.A.
Phylum: Actinobacteria
Class: Actinomycetia
Order: Streptomycetales
Family: Streptomycetaceae
Genus: Streptomyces
Species: Streptomyces lavendulae

Type(s) of Resistant Mechanism of This Molecule

  DISM: Drug Inactivation by Structure Modification

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Lestaurtinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Ovarian cancer [ICD-11: 2C73.0] [1]

• Sensitive Disease: Ovarian cancer [ICD-11: 2C73.0]
• Sensitive Drug: Lestaurtinib
• Molecule Alteration: Phosphorylation; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: JAK-STAT signaling pathway; Inhibition; hsa04630
• In Vitro Model: MDA-H2774 cells; Ascites; Homo sapiens (Human); CVCL_0420
• In Vitro Model: OVSAHO cells; Abdomen; Homo sapiens (Human); CVCL_3114
• In Vitro Model: SKOV-3 cells; Ovary; Homo sapiens (Human); CVCL_0532
• In Vitro Model: FT194 cells; Fallopian tube; Homo sapiens (Human); CVCL_UH58
• In Vitro Model: FT282 cells; Fallopian tube; Homo sapiens (Human); CVCL_A4AX
• Experiment for Molecule Alteration: RNA sequencing assay; RT-qPCR; Western blot assay
• Experiment for Drug Resistance: Proliferation assay; Cell cycle profiling assay; Apoptosis assay; Colony formation assay
• Mechanism Description: Through an unbiased drug screen, we identified the kinase inhibitor, lestaurtinib, as a potent antineoplastic agent for chemotherapy- and PARP-inhibitor (PARPi)-sensitive and -resistant ovarian cancer cells and patient derived xenografts (PDXs). RNA-sequencing revealed that lestaurtinib potently suppressed JAK/STAT signaling and lestaurtinib efficacy was shown to be directly related to JAK/STAT pathway activity in cell lines and PDX models. Most ovarian cancer cells exhibited constitutive JAK/STAT pathway activation and genetic loss of STAT1 and STAT3 resulted in growth inhibition. Lestaurtinib also displayed synergy when combined with cisplatin and olaparib, including in a model of PARPi resistance. In contrast, the most well-known JAK/STAT inhibitor, ruxolitinib, lacked antineoplastic activity against all ovarian cancer cell lines and PDX models tested. This divergent behavior was reflected in the ability of lestaurtinib to block both Y701/705 and S727 phosphorylation of STAT1 and STAT3, whereas ruxolitinib failed to block S727. Consistent with these findings, lestaurtinib additionally inhibited the serine/threonine kinases, JNK and ERK, leading to more complete suppression of STAT phosphorylation. Concordantly, combinatorial treatment with ruxolitinib and a JNK or ERK inhibitor resulted in synergistic antineoplastic effects at dose levels where the single agents were ineffective. Taken together, these findings indicate that lestaurtinib, and other treatments that converge on JAK/STAT signaling, are worthy of further pre-clinical and clinical exploration for the treatment of highly aggressive and advanced forms of ovarian cancer.

Investigative Drug(s) 1 drug(s) in total

Streptothricin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Disease Class: Streptomyces lavendulae infection [ICD-11: 1C43.13] [2]

• Resistant Disease: Streptomyces lavendulae infection [ICD-11: 1C43.13]
• Resistant Drug: Streptothricin
• Molecule Alteration: Expression; Inherence
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Streptomyces lividans strain Tk21; 1916
• In Vitro Model: Bacillus subtilis strain RM141; 1423
• In Vitro Model: Escherichia coli strain 5131-5; 562
• Experiment for Molecule Alteration: [a-32P] dCTP by the dideoxynucleoside triphosphate chain termination method assay
• Mechanism Description: The nucleotide sequence of the streptothricin acetyltransferase (STAT) gene from streptothricin-producing Streptomyces lavendulae predicts a 189-amino-acid protein of molecular weight 20,000, which is consistent with that determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified enzyme. By addition of promoter signals and a synthetic ribosome-binding (Shine-Dalgarno) sequence at an appropriate position upstream of the STAT translational start codon, the STAT gene confers streptothricin resistance on Escherichia coli and Bacillus subtilis.

Disease Class: Escherichia coli infection [ICD-11: 1A03.0] [2]

• Resistant Disease: Escherichia coli infection [ICD-11: 1A03.0]
• Resistant Drug: Streptothricin
• Molecule Alteration: Expression; Inherence
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Streptomyces lividans strain Tk21; 1916
• In Vitro Model: Bacillus subtilis strain RM141; 1423
• In Vitro Model: Escherichia coli strain 5131-5; 562
• Experiment for Molecule Alteration: [a-32P] dCTP by the dideoxynucleoside triphosphate chain termination method assay
• Mechanism Description: The nucleotide sequence of the streptothricin acetyltransferase (STAT) gene from streptothricin-producing Streptomyces lavendulae predicts a 189-amino-acid protein of molecular weight 20,000, which is consistent with that determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified enzyme. By addition of promoter signals and a synthetic ribosome-binding (Shine-Dalgarno) sequence at an appropriate position upstream of the STAT translational start codon, the STAT gene confers streptothricin resistance on Escherichia coli and Bacillus subtilis.

Disease Class: Bacillus subtilis infection [ICD-11: 1G40.1] [2]

• Resistant Disease: Bacillus subtilis infection [ICD-11: 1G40.1]
• Resistant Drug: Streptothricin
• Molecule Alteration: Expression; Inherence
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Streptomyces lividans strain Tk21; 1916
• In Vitro Model: Bacillus subtilis strain RM141; 1423
• In Vitro Model: Escherichia coli strain 5131-5; 562
• Experiment for Molecule Alteration: [a-32P] dCTP by the dideoxynucleoside triphosphate chain termination method assay
• Mechanism Description: The nucleotide sequence of the streptothricin acetyltransferase (STAT) gene from streptothricin-producing Streptomyces lavendulae predicts a 189-amino-acid protein of molecular weight 20,000, which is consistent with that determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified enzyme. By addition of promoter signals and a synthetic ribosome-binding (Shine-Dalgarno) sequence at an appropriate position upstream of the STAT translational start codon, the STAT gene confers streptothricin resistance on Escherichia coli and Bacillus subtilis.

References

• Ref 1: Lestaurtinib's antineoplastic activity converges on JAK/STAT signaling to inhibit treatment na?ve and therapy resistant forms ovarian cancer. NPJ Precis Oncol. 2025 Jul 11;9(1):236.
• Ref 2: Nucleotide sequence of the streptothricin acetyltransferase gene from Streptomyces lavendulae and its expression in heterologous hosts. J Bacteriol. 1987 May;169(5):1929-37. doi: 10.1128/jb.169.5.1929-1937.1987.