Bioprocessing of streptomycin MCQs With Answer

Introduction:

This question set focuses on the bioprocessing of streptomycin for M.Pharm students, covering upstream fermentation, strain improvement, metabolic precursors, process control, and downstream recovery. Emphasis is placed on practical and theoretical aspects: selection of Streptomyces strains, optimization of media and culture conditions, oxygen transfer and kLa considerations, fed-batch strategies, and biochemical regulation of streptomycin biosynthesis. Downstream topics include extraction, ion-exchange purification, crystallization as streptomycin sulfate, potency assays, and stability. These MCQs are designed to deepen understanding of how bioprocess parameters influence yield, quality, and scalability of industrial streptomycin production and to prepare students for process development and QA/QC challenges.

Q1. Which organism is the classical industrial producer of streptomycin used in commercial fermentation?

  • Escherichia coli
  • Streptomyces griseus
  • Bacillus subtilis
  • Staphylococcus aureus

Correct Answer: Streptomyces griseus

Q2. In streptomycin fermentation, which carbon source is commonly used to avoid catabolite repression and favor secondary metabolism?

  • High concentration glucose
  • Glycerol or controlled glucose feeding
  • Fructose at high feed rates
  • Pure sucrose in excess

Correct Answer: Glycerol or controlled glucose feeding

Q3. Which medium component is typically supplemented to provide nitrogen for amino-sugar precursors in streptomycin biosynthesis?

  • Trace minerals only
  • Ammonium salts or soybean meal hydrolysate
  • Sodium chloride
  • Polysorbate 80

Correct Answer: Ammonium salts or soybean meal hydrolysate

Q4. The primary biosynthetic precursor class required for streptomycin assembly includes which of the following?

  • Fatty acids
  • Amino sugars and streptidine derivatives
  • Polyketide backbones
  • Terpenoids

Correct Answer: Amino sugars and streptidine derivatives

Q5. During scale-up of streptomycin fermentation, which parameter is most critical to maintain similar oxygen transfer performance?

  • Impeller speed alone
  • kLa (volumetric oxygen transfer coefficient)
  • Headspace pressure
  • Vessel color

Correct Answer: kLa (volumetric oxygen transfer coefficient)

Q6. Which fermentation mode is frequently used to enhance streptomycin yield by minimizing substrate inhibition and catabolite repression?

  • Continuous chemostat with high dilution
  • Fed-batch with controlled substrate feeding
  • Static solid-state only
  • Batch with a single high-dose glucose spike

Correct Answer: Fed-batch with controlled substrate feeding

Q7. What is the typical form used for final pharmaceutical streptomycin preparations due to improved stability and solubility?

  • Free base streptomycin
  • Streptomycin sulfate
  • Streptomycin nitrate
  • Streptomycin acetate

Correct Answer: Streptomycin sulfate

Q8. Which downstream unit operation is commonly used first to recover streptomycin from clarified fermentation broth?

  • Direct crystallization from whole broth
  • Adsorption onto resin or ion-exchange from clarified broth
  • Lyophilization of crude broth
  • Soxhlet extraction

Correct Answer: Adsorption onto resin or ion-exchange from clarified broth

Q9. Which analytical method is standard for quantifying streptomycin potency in finished product quality control?

  • UV absorbance at 280 nm without reference
  • Microbial bioassay or HPLC with suitable derivatization
  • Gravimetric total solids
  • pH titration only

Correct Answer: Microbial bioassay or HPLC with suitable derivatization

Q10. Excessive antifoam addition in streptomycin fermentations can negatively affect which of the following?

  • Sterility only
  • Oxygen transfer and mass transfer rates
  • Genetic stability of Streptomyces
  • pH meter calibration

Correct Answer: Oxygen transfer and mass transfer rates

Q11. Which genetic approach is commonly used to increase streptomycin titers in industrial strains?

  • Random mutagenesis and selection for hyperproducers
  • Cloning into E. coli expression systems only
  • Knockout of primary metabolism strictly
  • Insertion of viral promoters into unrelated genes

Correct Answer: Random mutagenesis and selection for hyperproducers

Q12. Streptomycin biosynthesis gene clusters in Streptomyces are typically organized as:

  • Scattered single genes across the chromosome
  • Contiguous operons or gene clusters encoding enzymes, regulators, and resistance genes
  • Only plasmid-encoded genes
  • Exclusively ribosomal RNA genes

Correct Answer: Contiguous operons or gene clusters encoding enzymes, regulators, and resistance genes

Q13. Which process control strategy is most effective for maintaining dissolved oxygen at levels favorable for streptomycin production?

  • Fixed agitation and variable temperature
  • Cascade control adjusting agitation and aeration to a DO setpoint
  • Manual aeration only
  • Shut down aeration intermittently

Correct Answer: Cascade control adjusting agitation and aeration to a DO setpoint

Q14. During downstream purification, ion-exchange chromatography for streptomycin exploits which property of the molecule?

  • Hydrophobicity only
  • Basic amino groups and polycationic character at specific pH
  • High molecular weight aggregation
  • Intrinsic fluorescence

Correct Answer: Basic amino groups and polycationic character at specific pH

Q15. Which fermentation by-product or condition most commonly reduces streptomycin yield if not controlled?

  • Excess dissolved oxygen
  • Accumulation of organic acids and low pH
  • High phosphate buffering
  • Low biomass levels only

Correct Answer: Accumulation of organic acids and low pH

Q16. A common strategy to improve precursor supply for streptomycin biosynthesis is:

  • Supplementation with amino sugar precursors like streptose or glucose-6-phosphate derivatives
  • Complete carbon starvation
  • Removal of nitrogen sources during production phase
  • Adding non-metabolizable sugars

Correct Answer: Supplementation with amino sugar precursors like streptose or glucose-6-phosphate derivatives

Q17. Which stability factor is important for storage of streptomycin sulfate pharmaceutical formulations?

  • Extreme alkaline pH
  • Protection from high temperature and moisture
  • Exposure to strong oxidizing agents
  • Continuous light exposure

Correct Answer: Protection from high temperature and moisture

Q18. In bioprocess optimization studies, which design approach is effective for empirically identifying significant factors affecting streptomycin yield?

  • One-factor-at-a-time experiments only
  • Design of Experiments (DoE) such as factorial designs and response surface methodology
  • Random trial-and-error without statistical analysis
  • Only literature fixed recipes without experimentation

Correct Answer: Design of Experiments (DoE) such as factorial designs and response surface methodology

Q19. Which of the following best describes the mode of action of streptomycin relevant to its selection and potency assays?

  • Inhibition of cell wall synthesis
  • Irreversible binding to the 30S ribosomal subunit causing misreading of mRNA
  • Interference with folate metabolism
  • Disruption of ergosterol in membranes

Correct Answer: Irreversible binding to the 30S ribosomal subunit causing misreading of mRNA

Q20. Which process is typically used to obtain crystalline streptomycin sulfate suitable for pharmaceutical use after ion-exchange and concentration?

  • Direct spray-drying without crystallization
  • Controlled crystallization followed by filtration and drying
  • Gas-phase adsorption
  • Dry heat sterilization of liquid concentrate

Correct Answer: Controlled crystallization followed by filtration and drying

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