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Chymosin, Rennin, Rennet, Milk-Clotting Enzyme, Aspartic Protease, 9001-98-3

Chymosin, Rennin, Rennet, Milk-Clotting Enzyme, Aspartic Protease, 9001-98-3

CHYMOSIN (RENNET, MILK-CLOTTING ENZYME)

Chymosin / Rennin / Rennet / Milk-Clotting Enzyme / Aspartic Protease

  • CAS Number: 9001-98-3

  • EC Number: 232-645-0

  • Enzyme Class: EC 3.4.23.4

SECTION 1: PRODUCT DEFINITION AND CHEMICAL IDENTITY

Parameter Information
Product Name Chymosin
Other Names Rennin, Rennet, Milk-Clotting Enzyme, Aspartic Protease, Calf Rennet, Microbial Rennet
CAS Number 9001-98-3
EC Number (EINECS) 232-645-0
Enzyme Class Hydrolase (EC 3.4.23.4)
Systematic Name Aspartic protease (chymosin)
Chemical Structure Protein (polypeptide chain), globular structure, aspartic protease
Source Animal (calf stomach mucosa), Microbial (Aspergillus niger, Aspergillus oryzae, Rhizomucor miehei, Rhizomucor pusillus), Recombinant (genetically modified microorganisms)
Appearance Light brown to off-white powder or liquid formulation
Solubility Readily soluble in water
Molecular Weight 30,000 - 40,000 Da (chymosin); 30,000 - 45,000 Da (microbial rennet)
Protease Class Aspartic protease (acidic protease)

Description:
Chymosin (also known as rennin or rennet) is an aspartic protease enzyme that clots milk proteins (especially casein). Chymosin initiates clotting by hydrolyzing soluble κ-casein in milk. This reaction separates milk into curds and whey. In cheese production, it is used to clot milk, forming the structure and texture of cheese. Traditionally obtained from animal sources (calf stomach mucosa), microbial and recombinant chymosins are now widely used. Recombinant chymosin is chemically identical to animal chymosin and is preferred for vegetarian cheese production.

SECTION 2: SYNONYMS AND OTHER NAMES

Type Name
Common Names Chymosin, Rennin, Rennet, Milk-Clotting Enzyme, Calf Rennet
Enzymatic Names Aspartic protease, Milk-clotting enzyme, Coagulase
EC Number 3.4.23.4
CAS Number 9001-98-3
HS Code 3507.10.00
WGK Germany 1 (low hazard to water)

SECTION 3: ENZYMATIC STRUCTURE

3.1. Molecular Structure
Chymosin is an aspartic protease consisting of two main domains. It contains two lobes: an N-terminal and a C-terminal lobe. The active site is located between two aspartic acid residues (Asp-32 and Asp-215) in both lobes. The enzyme catalyzes the coagulation of milk proteins (especially κ-casein). Animal chymosin contains approximately 323 amino acids and has a molecular weight of 30,000-40,000 Da. Microbial rennets are aspartic proteases similar to chymosin but with different amino acid sequences.

3.2. Catalytic Mechanism
Chymosin initiates coagulation by hydrolyzing the Phe105-Met106 bond of κ-casein in milk:

  1. Substrate Binding: The κ-casein molecule binds to the active site of the enzyme.

  2. Catalytic Attack: Two aspartic acid residues (Asp-32 and Asp-215) in the active site activate a water molecule, which attacks the Phe105-Met106 bond of κ-casein.

  3. Bond Cleavage: The Phe105-Met106 bond is hydrolyzed, splitting κ-casein into two parts: para-casein and glycomacropeptide (GMP).

  4. Coagulation: Para-casein interacts with other casein molecules in the presence of calcium ions, forming a clot. GMP passes into the whey.

3.3. Molecular Weight
30,000 - 40,000 Da (chymosin); 30,000 - 45,000 Da (microbial rennet)

3.4. Basic Structural Properties

Property Description
Catalytic Domain Aspartic protease (two aspartic acid residues)
Active Site Asp-32 and Asp-215
Substrate Specificity κ-Casein (Phe105-Met106 bond)
Solubility Readily soluble in water
Isoelectric Point (pI) ~4.5 - 5.0
Thermal Stability Stable at 37°C; inactivated above 45°C

SECTION 4: PHYSICAL AND CHEMICAL PROPERTIES

Property Value
Appearance Light brown to off-white powder, granule, or liquid
Odor Slight fermented or characteristic (enzymatic) odor
Color (Powder) Light brown to off-white
Molecular Weight 30,000 - 40,000 Da (chymosin); 30,000 - 45,000 Da (microbial)
Isoelectric Point (pI) ~4.5 - 5.0
Solubility in Water Readily soluble
Solubility in Ethanol Insoluble (precipitated)
Solubility in Acetone Insoluble (precipitated)
Density (Powder) ~0.5 - 0.7 g/cm³ (uncompacted)
Loss on Drying (Powder) ≤ 8.0 %
Optimum pH 5.5 – 6.5
pH Stability 5.0 – 7.0
Optimum Temperature 30 – 37°C
Temperature Stability Stable at 37°C; activity decreases above 42°C; rapidly inactivated at 45°C
Calcium Requirement Calcium (Ca²⁺) ions are required for coagulation
Activity Inhibitors Heavy metals (Hg²⁺, Cu²⁺), SDS, Pepstatin A (aspartic protease inhibitor), EDTA
Activity Activators Calcium (Ca²⁺) ions, Sodium (Na⁺) ions

SECTION 5: ENZYMATIC ACTIVITY AND REACTION

Parameter Information
EC Number 3.4.23.4
Systematic Name Aspartic protease (chymosin)
Reaction κ-Casein + H₂O → Para-casein + Glycomacropeptide (GMP)
Substrate Specificity κ-Casein (Phe105-Met106 bond), α-casein (partially), β-casein (partially)
Cleavage Type Endopeptidase
Bond Specificity Phenylalanine-Methionine bond (Phe-Met)
Product Type Para-casein (forms clot), Glycomacropeptide (GMP)
Clotting Unit (U) 1 U = amount of enzyme that clots a specific amount of milk in 1 minute at pH 6.3 and 35°C (IMCU - International Milk Clotting Unit)
Specific Activity 50 - 500 IMCU/mg (depending on purity and source)
Activity Assay Milk clotting test (Berridge method), Spectrophotometric method (casein substrate)
Clotting Time Typically 5-30 minutes under standard conditions (35°C, pH 6.3); varies with enzyme dosage, temperature, and pH
Milk Type Cow milk, goat milk, sheep milk, buffalo milk

SECTION 6: REACTION MECHANISM

Chymosin catalyzes milk coagulation through a mechanism involving the following steps:

6.1. Substrate Binding
The κ-casein molecule (the soluble casein fraction in milk) binds to the active site of the enzyme. κ-Casein acts as a "protector" that stabilizes other casein molecules in milk and prevents coagulation.

6.2. Enzymatic Hydrolysis
Chymosin hydrolyzes the Phe105-Met106 bond of the κ-casein molecule. This splits κ-casein into two parts:

  • Para-casein (κ-casein amino acids 1-105): Participates in coagulation in the presence of calcium.

  • Glycomacropeptide (GMP, κ-casein amino acids 106-169): Soluble and passes into the whey.

6.3. Coagulation (Primary and Secondary Stages)

  • Primary Stage (Enzymatic): Hydrolysis of κ-casein removes the protective effect.

  • Secondary Stage (Chemical): Para-casein molecules interact with each other in the presence of calcium ions (Ca²⁺), forming a three-dimensional network. This network causes milk coagulation and curd formation.

6.4. Curd Syneresis
The formed curd contracts over time, expelling whey. This process determines the moisture content and texture of the cheese. Cutting and processing the curd affects the final product properties.

SECTION 7: REACTION EQUATIONS

7.1. κ-Casein Hydrolysis (Main Reaction)
κ-Casein + H₂O → Para-casein + Glycomacropeptide (GMP)

7.2. Coagulation Reaction
Para-casein + Ca²⁺ → Para-casein Calcium Complex (Clot)

7.3. Whey Formation
Milk + Chymosin → Curd (Para-casein + Ca²⁺) + Whey (GMP + Lactose + Minerals)

7.4. Enzyme Inactivation (Thermal)
Chymosin (active) → Chymosin (inactive) (≥45°C, 10-15 minutes)

7.5. Enzyme Inhibition (Pepstatin A)
Chymosin + Pepstatin A → Chymosin-Pepstatin A Complex (inactive)

SECTION 8: CHYMOSIN TYPES

Type Source Optimum pH Optimum Temp. Clotting Activity Proteolytic Activity Application Area
Animal Chymosin Calf stomach 5.5-6.0 35-37°C High Low Traditional cheese
Microbial Rennet Rhizomucor miehei 5.5-6.5 35-40°C Medium-High Medium Cheese production
Microbial Rennet Aspergillus niger 4.5-5.5 30-35°C Medium High Cheese production
Recombinant Chymosin Genetically modified microorganisms (E. coli, Pichia pastoris) 5.5-6.5 30-37°C High Low Vegetarian cheese
Animal Rennet (Mixture) Calf, lamb, goat stomach 5.5-6.5 30-37°C Medium-High Medium Traditional cheese
Plant Rennet Fig, papaya (papain) 5.0-6.0 30-35°C Low-Medium High Specialty cheeses

SECTION 9: APPLICATIONS AND INDUSTRIAL USES

9.1. Cheese Production

Application Function Typical Usage Condition
Milk Clotting Clots milk, forming cheese curd and whey. 0.01-0.05% (milk weight); 30-37°C; pH 6.2-6.6; 30-60 minutes
Cheese Texture Determines the structure, texture, and elasticity of cheese. Depends on milk type and cheese variety
Cheese Yield Increases cheese yield by minimizing casein loss. Optimum clotting conditions
Cheese Ripening Contributes to flavor development through proteolytic activity during cheese ripening. Depends on cheese variety

Example Recipe – Cheese Clotting (Cow Milk):

  • Cow milk: 1000 L

  • Chymosin (Recombinant): 10-50 g (depending on activity)

  • Calcium chloride (CaCl₂): 10-20 g (optional)

  • Application temperature: 30-35°C

  • Clotting time: 30-60 minutes

Heat milk to 30-35°C. Optionally add calcium chloride (to optimize milk's calcium content). Dissolve chymosin in a small amount of cold water and add to milk. Stir and leave to clot for the specified time. Check clot formation and cut the curd.

9.2. Cheese Varieties

Cheese Variety Chymosin Type Clotting Conditions Characteristics
Hard Cheese (Cheddar, Parmesan) Recombinant / Animal 30-32°C; 45-60 minutes Hard texture, long ripening
Soft Cheese (Camembert, Brie) Microbial / Recombinant 30-35°C; 30-45 minutes Soft texture, short ripening
Semi-Hard Cheese (Gouda, Edam) Recombinant / Animal 30-32°C; 40-50 minutes Medium-hard texture
Fresh Cheese (Mozzarella, Ricotta) Microbial / Recombinant 35-37°C; 20-30 minutes Elastic, fresh texture
Goat Cheese Animal / Recombinant 30-35°C; 30-60 minutes Soft, creamy texture

9.3. Dairy Products and Protein Coagulation

Application Function Typical Usage Condition
Casein Production Coagulation for casein isolation from milk. 30-35°C; pH 6.2-6.6
Milk Protein Concentrates Concentration of milk proteins through coagulation. 30-35°C; pH 6.2-6.6
Yogurt (Texture Improvement) Casein modification to improve yogurt consistency. 30-35°C; pH 5.5-6.0
Whey Protein Coagulation of whey proteins. 30-35°C; pH 6.0-6.5

9.4. Pharmaceutical and Biotechnology

Application Function Typical Usage Condition
Protein Modification Enzymatic modification of specific proteins. Optimized conditions
Biocatalysis Biocatalytic reactions as aspartic protease. 30-37°C; pH 5.5-6.5
Protein Hydrolysates Production of casein hydrolysates. 30-37°C; pH 5.5-6.5

9.5. Other Applications

Application Function
Research and Development Dairy product and protein research.
Quality Control Testing clotting quality of milk and dairy products.
Food Analysis Casein determination and protein analysis.
Enzyme Standardization Standardization of clotting activity (IMCU).

SECTION 10: ALTERNATIVES AND COMPARISON

10.1. Animal Chymosin vs Recombinant Chymosin

Property Animal Chymosin Recombinant Chymosin
Advantages Traditional; natural source; well-characterized Vegetarian; consistent quality; high purity; sustainable; no animal content
Disadvantages Animal source; variable quality; limited availability; more expensive Chemically identical; may not be considered "natural" by some consumers
Selection Preferred for traditional cheese production and "natural" labeling Preferred for vegetarian cheese, industrial production, and consistent quality

10.2. Chymosin vs Microbial Rennet

Property Chymosin Microbial Rennet
Advantages High clotting/proteolytic activity ratio; specific; less bitter peptide formation Lower cost; high availability; long shelf life
Disadvantages Higher cost; animal source (traditional) Higher proteolytic activity; risk of bitter peptide formation; less specific
Selection Preferred for high-quality, long-ripened cheeses Preferred for soft and semi-hard cheeses, low-cost production

10.3. Chymosin vs Plant Rennet (Papain, Ficin, Bromelain)

Property Chymosin Plant Rennet
Advantages Specific; high clotting activity; low bitterness; consistent quality Plant-based; vegetarian; natural; traditional
Disadvantages Animal or recombinant source; high cost Low clotting activity; high proteolytic activity; bitter peptide formation; variable quality
Selection Preferred for industrial cheese production Preferred for specialty cheeses, small-scale production, and traditional methods

10.4. Chymosin vs Acid Coagulation

Property Chymosin Acid Coagulation
Advantages Specific; controlled coagulation; soft curd; high yield Simple; low cost; fast
Disadvantages High cost; temperature and pH sensitivity Hard curd; acidic taste; low yield; less controlled
Selection Preferred for cheese production Preferred for fresh cheeses, casein production, and laboratory applications

SECTION 11: TOXICOLOGY AND SAFETY

11.1. Acute Toxicity

Parameter Value
Acute Oral Toxicity (LD50, Rat) Practically non-toxic (> 5,000 mg/kg)
Acute Dermal Toxicity Low risk (> 2,000 mg/kg)
Acute Inhalation Toxicity Powder form may cause respiratory sensitization
Eye Irritation Mild to moderate irritant
Skin Irritation Mild irritant; some forms may be sensitizing
Respiratory Sensitization May cause occupational asthma upon repeated exposure (enzyme dust)
Metabolism Enzyme protein is digested in the gastrointestinal tract and metabolized to amino acids
Allergenicity Caution for individuals with milk allergy (risk of milk protein contamination)

11.2. Regulatory Status

Parameter Information
FDA GRAS (Generally Recognized As Safe) - 21 CFR 184.1685
EFSA Approved as a food enzyme; safety assessment completed
JECFA Acceptable as a food additive; specifications established
Kosher Certification Available for microbial and recombinant forms
Halal Certification Available for microbial and recombinant forms
Vegetarian Recombinant and microbial forms are vegetarian; animal form is not
Vegan Recombinant and microbial forms are vegan; animal form is not

SECTION 12: GHS CLASSIFICATION (Powder Form)

Hazard Class Category H-Statement
Respiratory Sensitization Category 1 H334: May cause allergy or asthma symptoms if inhaled
Eye Irritation Category 2 H319: Causes serious eye irritation
Specific Target Organ Toxicity (STOT SE) Category 3 H335: May cause respiratory irritation

Signal Word: Danger

Hazard Pictograms: GHS07 (Exclamation mark), GHS08 (Health Hazard)

Hazard Statements (H-Codes):

  • H334: May cause allergy or asthma symptoms if inhaled

  • H319: Causes serious eye irritation

  • H335: May cause respiratory irritation

Safety Statements (Historical):

Code Statement
S22 Do not breathe dust.
S24/25 Avoid contact with skin and eyes.
S26 In case of contact with eyes, rinse immediately with plenty of water and seek medical advice.
S36/37/39 Wear suitable protective clothing, gloves, and eye/face protection.

SECTION 13: PRECAUTIONARY STATEMENTS (P-CODES)

Code Statement
P260 Do not breathe dust.
P264 Wash hands thoroughly after handling.
P271 Use only outdoors or in a well-ventilated area.
P280 Wear protective gloves/protective clothing/eye protection/face protection.
P302+P352 IF ON SKIN: Wash with plenty of soap and water.
P304+P340 IF INHALED: Remove person to fresh air and keep comfortable for breathing.
P305+P351+P338 IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present.
P337+P313 If eye irritation persists: Get medical advice/attention.
P342+P311 If experiencing respiratory symptoms: Call a POISON CENTER/doctor.
P403+P233 Store in a well-ventilated place. Keep container tightly closed.
P501 Dispose of contents/container in accordance with local regulations.

SECTION 14: FIRST AID MEASURES

Exposure Route Action to Take
Inhalation Remove from dusty environment. Move to fresh air. If breathing difficulty occurs, seek medical attention. If symptoms persist, consult a doctor.
Skin Contact Wash with plenty of soap and water. Remove contaminated clothing. If redness or irritation occurs, seek medical attention.
Eye Contact Rinse cautiously with water for at least 15 minutes. Remove contact lenses if present. If irritation persists, seek medical attention.
Ingestion Rinse mouth. Drink plenty of water. Do NOT induce vomiting. If unconscious, do not give anything by mouth. Seek medical attention.
Note In case of allergic reaction (respiratory difficulty, skin rash), seek immediate medical attention. Caution for individuals with milk allergy.

SECTION 15: FIREFIGHTING MEASURES

Parameter Information
Fire Hazard Organic dust may pose a fire hazard; dust clouds may be explosive in air
Suitable Extinguishing Media Water spray, CO₂, dry chemical powder, alcohol-resistant foam
Specific Hazards Thermal decomposition produces toxic gases (CO, CO₂, nitrogen oxides, sulfur oxides)
Protective Equipment Self-contained breathing apparatus (SCBA), full protective clothing
Special Precautions Avoid dust cloud formation. Cool containers with water spray.
Explosion Risks Dust/air mixtures may be explosive. Provide ventilation and ignition source control.

SECTION 16: ACCIDENTAL RELEASE MEASURES

Parameter Information
Personal Protection Protective goggles, chemical-resistant gloves, dust mask (P2/P3), coverall
Ventilation Increase ventilation; use local exhaust; prevent dust from dispersing into air
Containment Absorb with inert material (sand, vermiculite); prevent dust spread
Cleaning Methods Collect with absorbent material. Use vacuum cleaner to prevent dust formation. Avoid sweeping as it may raise dust; wet cleaning is preferred.
Environmental Precautions Prevent entry into sewers, drains, and water bodies. Prevent contamination of soil and surface water.
Waste Disposal Dispose of in accordance with local regulations. Collect contaminated materials in closed containers.

SECTION 17: STORAGE AND SHELF LIFE

Parameter Information
Storage Conditions Store in a cool, dry, well-ventilated area. Protect from direct sunlight. Protect from moisture.
Temperature Recommended: 4-25°C. For long-term storage, 4°C (refrigeration) is recommended. Avoid freezing.
Container Requirements Tightly closed, moisture-resistant containers. Use HDPE, PP, or aluminum containers.
Materials to Avoid High temperature (>40°C), high humidity, direct sunlight, strong oxidizers, heavy metals (Hg²⁺, Cu²⁺).
Material Compatibility HDPE, PP, aluminum, stainless steel. Avoid: Copper, zinc, iron (may cause activity loss).
Shelf Life 12-24 months (in unopened original packaging, under recommended storage conditions)
Stability Note Hygroscopic; absorbs moisture. Store in tightly closed containers to prevent activity loss. Enzyme activity declines at elevated temperatures. Calcium presence may improve stability.

SECTION 18: PACKAGING OPTIONS

Packaging Type Quantity Material
Powder Form 1 kg, 5 kg, 10 kg, 20 kg, 25 kg Aluminum foil bag / HDPE drum / Multi-layer kraft bag
Liquid Form 1 L, 5 L, 10 L, 20 L, 200 L HDPE bottle / HDPE drum / IBC tank
Bulk (Powder) 500 – 1000 kg Big bag / FIBC
Bulk (Liquid) 1000 L IBC Tank
Small Containers 50 g, 100 g, 500 g Aluminum foil bag / HDPE bottle

SECTION 19: TRANSPORT INFORMATION

Parameter Information
UN Number Not applicable (not classified as dangerous goods)
Hazard Class Not classified as dangerous for transport
Packing Group Not applicable
ADR/RID Not regulated
IMDG Code Not regulated
IATA (Air) Not regulated (consult airline for powder form)
Marine Pollutant No
Transport Temperature Ambient temperature; protect from moisture and direct sunlight.
Special Transport Conditions Prevent dust dispersion from powder form. Prevent leakage from liquid form.

SECTION 20: ENVIRONMENTAL INFORMATION

Parameter Information
Aquatic Toxicity Low toxicity to aquatic organisms (EC50 > 100 mg/L)
Biodegradability Readily biodegradable (due to protein structure)
Bioaccumulation Low potential (proteins generally do not bioaccumulate)
Mobility in Soil Moderate; protein structure degrades in soil
Vapor Behavior Non-volatile (powder form) / Low vapor pressure (liquid form)
WGK Germany 1 (low hazard to water)
Ecotoxicology Low toxicity to soil organisms; does not affect beneficial microorganisms
Waste Disposal Incineration or disposal in accordance with local regulations; do not discharge into sewers

SECTION 21: REGULATORY STATUS

Region / Authority Status
European Union (EFSA) Approved as a food enzyme; safety assessment completed
European Union (REACH) Registered; approved for use as a food enzyme
USA (FDA) GRAS (21 CFR 184.1685)
Turkey Approved as a food enzyme; complies with Turkish Food Codex
JECFA Acceptable as a food additive; specifications established
Kosher Certification Available for microbial and recombinant forms
Halal Certification Available for microbial and recombinant forms
Vegetarian Recombinant and microbial forms are vegetarian
Vegan Recombinant and microbial forms are vegan

SECTION 22: FREQUENTLY ASKED QUESTIONS (FAQ)

Q1: Is chymosin safe?
A1: Yes. Chymosin is classified as GRAS (Generally Recognized As Safe) by the FDA and approved as a food enzyme by EFSA. It has been safely used in cheese production for many years. However, the powder form may cause allergic reactions when inhaled, so appropriate personal protective equipment should be used.

Q2: What is the difference between chymosin and rennet?
A2: Chymosin is the main enzyme that clots milk. Rennet is traditionally obtained from calf stomach and contains chymosin and other proteases (pepsin). Today, the term "rennet" is used as a general term for all milk-clotting enzymes. Recombinant chymosin is the active component of animal rennet.

Q3: Is chymosin suitable for vegetarian products?
A3: Recombinant chymosin (produced by microbial fermentation) and microbial rennet are vegetarian and can be halal/kosher certified. Animal-derived chymosin (from calf stomach) is not vegetarian. Relevant certificates can be obtained from manufacturers.

Q4: Why is chymosin used in cheese production?
A4: Chymosin hydrolyzes κ-casein in milk, causing milk coagulation. This initiates the formation of cheese curd and whey. Chymosin is the most important enzyme that determines the structure, texture, and ripening properties of cheese. Different chymosin types and dosages are used for different cheese varieties.

Q5: Is chymosin suitable for vegan products?
A5: Recombinant chymosin (produced by microbial fermentation) is vegan. Animal-derived chymosin (from calf stomach) is not vegan. Recombinant chymosin is produced using genetically modified microorganisms and contains no animal ingredients. It is preferred for vegetarian and vegan cheese production.

Q6: How should chymosin be stored?
A6: Store in a cool (preferably 4-25°C), dry, well-ventilated area in tightly closed containers. Moisture, high temperature (>40°C), and direct sunlight cause activity loss. Contact with heavy metals (copper, mercury) should be avoided. Long-term storage at 4°C is recommended.

Q7: What are the optimum working conditions for chymosin?
A7: The optimum pH of chymosin is between 5.5-6.5, and the optimum temperature is between 30-37°C. Calcium ions (Ca²⁺) are required for coagulation. The enzyme is stable up to 37°C, activity decreases above 42°C, and it is rapidly inactivated at 45°C. Milk pH, temperature, and calcium content directly affect clotting time.

Q8: How does chymosin affect cheese yield?
A8: Chymosin increases cheese yield by minimizing casein loss. Under optimum clotting conditions (correct temperature, pH, calcium, and enzyme dosage), all casein is converted to curd. Excessive enzyme use or incorrect conditions can cause casein loss and low yield. Recombinant chymosin provides yield increase due to its high purity.

Q9: What is the difference between recombinant chymosin and animal chymosin?
A9: Recombinant chymosin is produced using genetically modified microorganisms (E. coli, Pichia pastoris, Aspergillus niger) and is chemically identical to animal chymosin. Animal chymosin is obtained from calf stomach. Recombinant chymosin is vegetarian and vegan as it is not animal-derived, has more consistent quality, and is sustainable.

Q10: What are the effects of inhaling chymosin powder?
A10: Chymosin powder, when inhaled, can cause allergic reactions, asthma-like symptoms, and respiratory tract irritation. Occupational asthma can develop upon repeated exposure to enzyme dust in cheese production facilities. Therefore, a dust mask (P2/P3) must always be used when handling the powder form, and local exhaust ventilation should be provided. Caution for individuals with milk allergy.

SECTION 23: QUICK REFERENCE TABLE

Property Value
CAS Number 9001-98-3
EC Number 232-645-0
EC Class 3.4.23.4
Systematic Name Aspartic protease (chymosin)
Appearance Light brown powder or liquid
Odor Slight fermented / characteristic
Molecular Weight 30,000 - 40,000 Da
Optimum pH 5.5 – 6.5
Optimum Temperature 30 – 37°C
Solubility in Water Readily soluble
Substrate κ-Casein
Product Para-casein + Glycomacropeptide (GMP)
Calcium Requirement Yes (Ca²⁺)
Activity ≥ 100,000 IMCU/g (powder) / ≥ 5,000 IMCU/mL (liquid)
Shelf Life 12-24 months
Primary Uses Cheese production, milk clotting
UN Number Not applicable
WGK Germany 1

SECTION 24: CRITICAL WARNINGS AND BEST PRACTICES

CRITICAL WARNINGS:

  1. Dust Control and Respiratory Sensitization: Chymosin powder can cause occupational asthma upon repeated exposure. Use local exhaust ventilation to prevent dust dispersion and always wear a dust mask (P2/P3). Liquid formulations are safer than powder forms.

  2. Calcium Requirement: Chymosin requires calcium ions (Ca²⁺) for coagulation. Milk's natural calcium content may be insufficient; therefore, calcium chloride (CaCl₂) may need to be added. Optimum calcium concentration is ~1.5-2.5 mM.

  3. Activity Loss - Temperature: Chymosin is rapidly and irreversibly inactivated above 45°C. Strictly maintain application temperatures within the optimum range (30-37°C). Temperature control is critical in cheese production.

  4. Activity Loss - pH: Chymosin loses stability below pH 5.0 or above pH 7.0. Maintain application pH within the optimum range (5.5-6.5). Excessively acidic or basic conditions cause permanent enzyme inactivation.

  5. Milk Type and Quality: Different milk types (cow, goat, sheep, buffalo) show different clotting properties. Milk pH, calcium content, and protein composition affect clotting time. Optimum conditions should be determined for each milk type.

  6. Activity Loss - Heavy Metals: Mercury (Hg²⁺), copper (Cu²⁺), and other heavy metals inhibit chymosin. Avoid these metals in equipment that comes into contact with the enzyme. Stainless steel, HDPE, or glass materials are preferred.

  7. Food Grade: Only FDA/EFSA-approved food-grade chymosin meeting specifications should be used in food applications. Industrial grade enzymes may contain impurities and are not suitable for human consumption.

  8. Proteolytic Activity: Chymosin has low proteolytic activity (compared to pepsin). This reduces bitter peptide formation in cheese. Microbial rennets may have higher proteolytic activity. The correct enzyme should be selected according to cheese variety.

BEST PRACTICE RECOMMENDATIONS:

  • Storage: Store in a cool (4-25°C), dry, well-ventilated area in tightly closed containers. For long-term storage, +4°C (refrigeration) is recommended. Use within a short period after opening.

  • Handling: Use protective gloves, dust mask (P2/P3), and protective goggles. To prevent dust dispersion, preferably use liquid formulations. Prepare working solutions fresh for each application.

  • Milk Preparation: Heat milk to optimum temperature (30-37°C). If necessary, add calcium chloride (CaCl₂). Maintain milk pH between 6.2-6.6. Post-pasteurization milk may have altered clotting properties.

  • Dosage: Calculate the correct dosage according to enzyme activity (IMCU units). Check enzyme activity for each batch. Start with low dosage and adjust based on results. Typical dosage ranges are 0.01-0.05% of milk weight.

  • Clotting Control: Regularly check clotting time. Optimum clotting time is 30-60 minutes. Evaluate curd consistency and firmness. Continue processing after cutting the curd.

  • Enzyme Inactivation: Inactivate the enzyme by heat treatment (≥45°C, 10-15 minutes) after clotting is complete. Heat treatments applied during cheese processing will inactivate the enzyme.

  • Quality Control: Perform activity testing for each batch. Maintain production and handling hygiene to prevent microbiological contamination. Monitor clotting time, curd firmness, and cheese yield for consistent product quality.

  • Waste Management: Dispose of enzyme and contaminated materials in accordance with local regulations. Do not discharge into sewers. If released into wastewater, inactivate the enzyme by heat treatment before disposal.

LEGAL DISCLAIMER:

This Technical Data Sheet (TDS) is for informational purposes only and is prepared based on available technical data. The user is responsible for determining the suitability of the product for their specific application and for complying with all local, national, and international regulations. For complete safety, storage, handling, transport, waste, and regulatory compliance information, refer to the official Safety Data Sheet (SDS/MSDS) provided by the manufacturer/supplier. Chymosin powder may cause sensitization when inhaled; appropriate protective equipment should be used. Caution for individuals with milk allergy. This document does not replace professional or medical advice.

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