@synsci/cli-darwin-x64 1.1.76 → 1.1.78

package/bin/skills/brenda-database/scripts/brenda_queries.py

@@ -0,0 +1,844 @@
+"""
+BRENDA Database Query Utilities
+
+This module provides high-level functions for querying and analyzing
+enzyme data from the BRENDA database using the SOAP API.
+
+Key features:
+- Parse BRENDA response data entries
+- Search for enzymes by substrate/product
+- Compare enzyme properties across organisms
+- Retrieve kinetic parameters and environmental conditions
+- Analyze substrate specificity and inhibition
+- Support for enzyme engineering and pathway design
+- Export data in various formats
+
+Installation:
+    uv pip install zeep requests pandas
+
+Usage:
+    from scripts.brenda_queries import search_enzymes_by_substrate, compare_across_organisms
+
+    enzymes = search_enzymes_by_substrate("glucose", limit=20)
+    comparison = compare_across_organisms("1.1.1.1", ["E. coli", "S. cerevisiae"])
+"""
+
+import re
+import time
+import json
+import csv
+from typing import List, Dict, Any, Optional, Tuple
+from pathlib import Path
+
+try:
+    from zeep import Client, Settings
+    from zeep.exceptions import Fault, TransportError
+    ZEEP_AVAILABLE = True
+except ImportError:
+    print("Warning: zeep not installed. Install with: uv pip install zeep")
+    ZEEP_AVAILABLE = False
+
+try:
+    import requests
+    REQUESTS_AVAILABLE = True
+except ImportError:
+    print("Warning: requests not installed. Install with: uv pip install requests")
+    REQUESTS_AVAILABLE = False
+
+try:
+    import pandas as pd
+    PANDAS_AVAILABLE = True
+except ImportError:
+    print("Warning: pandas not installed. Install with: uv pip install pandas")
+    PANDAS_AVAILABLE = False
+
+# Import the brenda_client from the project root
+import sys
+sys.path.append(str(Path(__file__).parent.parent.parent.parent))
+
+try:
+    from brenda_client import get_km_values, get_reactions, call_brenda
+    BRENDA_CLIENT_AVAILABLE = True
+except ImportError:
+    print("Warning: brenda_client not available")
+    BRENDA_CLIENT_AVAILABLE = False
+
+
+def validate_dependencies():
+    """Validate that required dependencies are installed."""
+    missing = []
+    if not ZEEP_AVAILABLE:
+        missing.append("zeep")
+    if not REQUESTS_AVAILABLE:
+        missing.append("requests")
+    if not BRENDA_CLIENT_AVAILABLE:
+        missing.append("brenda_client")
+    if missing:
+        raise ImportError(f"Missing required dependencies: {', '.join(missing)}")
+
+
+def parse_km_entry(entry: str) -> Dict[str, Any]:
+    """Parse a BRENDA Km value entry into structured data."""
+    if not entry or not isinstance(entry, str):
+        return {}
+
+    parsed = {}
+    parts = entry.split('#')
+
+    for part in parts:
+        if '*' in part:
+            key, value = part.split('*', 1)
+            parsed[key.strip()] = value.strip()
+
+    # Extract numeric values from kmValue
+    if 'kmValue' in parsed:
+        km_value = parsed['kmValue']
+        # Extract first numeric value (in mM typically)
+        numeric_match = re.search(r'(\d+\.?\d*)', km_value)
+        if numeric_match:
+            parsed['km_value_numeric'] = float(numeric_match.group(1))
+
+    # Extract pH from commentary
+    if 'commentary' in parsed:
+        commentary = parsed['commentary']
+        ph_match = re.search(r'pH\s*([0-9.]+)', commentary)
+        if ph_match:
+            parsed['ph'] = float(ph_match.group(1))
+
+        temp_match = re.search(r'(\d+)\s*°?C', commentary)
+        if temp_match:
+            parsed['temperature'] = float(temp_match.group(1))
+
+    return parsed
+
+
+def parse_reaction_entry(entry: str) -> Dict[str, Any]:
+    """Parse a BRENDA reaction entry into structured data."""
+    if not entry or not isinstance(entry, str):
+        return {}
+
+    parsed = {}
+    parts = entry.split('#')
+
+    for part in parts:
+        if '*' in part:
+            key, value = part.split('*', 1)
+            parsed[key.strip()] = value.strip()
+
+    # Parse reaction equation
+    if 'reaction' in parsed:
+        reaction = parsed['reaction']
+        # Extract reactants and products
+        if '<=>' in reaction:
+            reactants, products = reaction.split('<=>', 1)
+        elif '->' in reaction:
+            reactants, products = reaction.split('->', 1)
+        elif '=' in reaction:
+            reactants, products = reaction.split('=', 1)
+        else:
+            reactants, products = reaction, ''
+
+        parsed['reactants'] = [r.strip() for r in reactants.split('+')]
+        parsed['products'] = [p.strip() for p in products.split('+')]
+
+    return parsed
+
+
+def extract_organism_data(entry: str) -> Dict[str, Any]:
+    """Extract organism-specific information from BRENDA entry."""
+    parsed = parse_km_entry(entry) if 'kmValue' in entry else parse_reaction_entry(entry)
+
+    if 'organism' in parsed:
+        return {
+            'organism': parsed['organism'],
+            'ec_number': parsed.get('ecNumber', ''),
+            'substrate': parsed.get('substrate', ''),
+            'km_value': parsed.get('kmValue', ''),
+            'km_numeric': parsed.get('km_value_numeric', None),
+            'ph': parsed.get('ph', None),
+            'temperature': parsed.get('temperature', None),
+            'commentary': parsed.get('commentary', ''),
+            'literature': parsed.get('literature', '')
+        }
+
+    return {}
+
+
+def search_enzymes_by_substrate(substrate: str, limit: int = 50) -> List[Dict[str, Any]]:
+    """Search for enzymes that act on a specific substrate."""
+    validate_dependencies()
+
+    enzymes = []
+
+    # Search for Km values with the substrate
+    try:
+        km_data = get_km_values("*", substrate=substrate)
+        time.sleep(0.5)  # Rate limiting
+
+        for entry in km_data[:limit]:
+            parsed = parse_km_entry(entry)
+            if parsed:
+                enzymes.append({
+                    'ec_number': parsed.get('ecNumber', ''),
+                    'organism': parsed.get('organism', ''),
+                    'substrate': parsed.get('substrate', ''),
+                    'km_value': parsed.get('kmValue', ''),
+                    'km_numeric': parsed.get('km_value_numeric', None),
+                    'commentary': parsed.get('commentary', '')
+                })
+    except Exception as e:
+        print(f"Error searching enzymes by substrate: {e}")
+
+    # Remove duplicates based on EC number and organism
+    unique_enzymes = []
+    seen = set()
+    for enzyme in enzymes:
+        key = (enzyme['ec_number'], enzyme['organism'])
+        if key not in seen:
+            seen.add(key)
+            unique_enzymes.append(enzyme)
+
+    return unique_enzymes[:limit]
+
+
+def search_enzymes_by_product(product: str, limit: int = 50) -> List[Dict[str, Any]]:
+    """Search for enzymes that produce a specific product."""
+    validate_dependencies()
+
+    enzymes = []
+
+    # Search for reactions containing the product
+    try:
+        # This is a simplified approach - in practice you might need
+        # more sophisticated pattern matching for products
+        reactions = get_reactions("*", reaction=f"*{product}*")
+        time.sleep(0.5)  # Rate limiting
+
+        for entry in reactions[:limit]:
+            parsed = parse_reaction_entry(entry)
+            if parsed and 'products' in parsed:
+                # Check if our target product is in the products list
+                if any(product.lower() in prod.lower() for prod in parsed['products']):
+                    enzymes.append({
+                        'ec_number': parsed.get('ecNumber', ''),
+                        'organism': parsed.get('organism', ''),
+                        'reaction': parsed.get('reaction', ''),
+                        'reactants': parsed.get('reactants', []),
+                        'products': parsed.get('products', []),
+                        'commentary': parsed.get('commentary', '')
+                    })
+    except Exception as e:
+        print(f"Error searching enzymes by product: {e}")
+
+    return enzymes[:limit]
+
+
+def compare_across_organisms(ec_number: str, organisms: List[str]) -> List[Dict[str, Any]]:
+    """Compare enzyme properties across different organisms."""
+    validate_dependencies()
+
+    comparison = []
+
+    for organism in organisms:
+        try:
+            # Get Km data for this organism
+            km_data = get_km_values(ec_number, organism=organism)
+            time.sleep(0.5)  # Rate limiting
+
+            if km_data:
+                # Calculate statistics
+                numeric_kms = []
+                phs = []
+                temperatures = []
+
+                for entry in km_data:
+                    parsed = parse_km_entry(entry)
+                    if 'km_value_numeric' in parsed:
+                        numeric_kms.append(parsed['km_value_numeric'])
+                    if 'ph' in parsed:
+                        phs.append(parsed['ph'])
+                    if 'temperature' in parsed:
+                        temperatures.append(parsed['temperature'])
+
+                org_data = {
+                    'organism': organism,
+                    'ec_number': ec_number,
+                    'data_points': len(km_data),
+                    'average_km': sum(numeric_kms) / len(numeric_kms) if numeric_kms else None,
+                    'min_km': min(numeric_kms) if numeric_kms else None,
+                    'max_km': max(numeric_kms) if numeric_kms else None,
+                    'optimal_ph': sum(phs) / len(phs) if phs else None,
+                    'optimal_temperature': sum(temperatures) / len(temperatures) if temperatures else None,
+                    'temperature_range': (min(temperatures), max(temperatures)) if temperatures else None
+                }
+
+                comparison.append(org_data)
+            else:
+                comparison.append({
+                    'organism': organism,
+                    'ec_number': ec_number,
+                    'data_points': 0,
+                    'note': 'No data found'
+                })
+
+        except Exception as e:
+            print(f"Error comparing organism {organism}: {e}")
+            comparison.append({
+                'organism': organism,
+                'ec_number': ec_number,
+                'error': str(e)
+            })
+
+    return comparison
+
+
+def get_organisms_for_enzyme(ec_number: str) -> List[str]:
+    """Get list of organisms that have data for a specific enzyme."""
+    validate_dependencies()
+
+    try:
+        km_data = get_km_values(ec_number)
+        time.sleep(0.5)  # Rate limiting
+
+        organisms = set()
+        for entry in km_data:
+            parsed = parse_km_entry(entry)
+            if 'organism' in parsed:
+                organisms.add(parsed['organism'])
+
+        return sorted(list(organisms))
+
+    except Exception as e:
+        print(f"Error getting organisms for enzyme {ec_number}: {e}")
+        return []
+
+
+def get_environmental_parameters(ec_number: str) -> Dict[str, Any]:
+    """Get environmental parameters (pH, temperature) for an enzyme."""
+    validate_dependencies()
+
+    try:
+        km_data = get_km_values(ec_number)
+        time.sleep(0.5)  # Rate limiting
+
+        phs = []
+        temperatures = []
+        ph_stabilities = []
+        temp_stabilities = []
+
+        for entry in km_data:
+            parsed = parse_km_entry(entry)
+
+            if 'ph' in parsed:
+                phs.append(parsed['ph'])
+            if 'temperature' in parsed:
+                temperatures.append(parsed['temperature'])
+
+            # Check commentary for stability information
+            commentary = parsed.get('commentary', '').lower()
+            if 'stable' in commentary and 'ph' in commentary:
+                # Extract pH stability range
+                ph_range_match = re.search(r'ph\s*([\d.]+)\s*[-–]\s*([\d.]+)', commentary)
+                if ph_range_match:
+                    ph_stabilities.append((float(ph_range_match.group(1)), float(ph_range_match.group(2))))
+
+            if 'stable' in commentary and ('temp' in commentary or '°c' in commentary):
+                # Extract temperature stability
+                temp_match = re.search(r'(\d+)\s*[-–]\s*(\d+)\s*°?c', commentary)
+                if temp_match:
+                    temp_stabilities.append((int(temp_match.group(1)), int(temp_match.group(2))))
+
+        params = {
+            'ec_number': ec_number,
+            'data_points': len(km_data),
+            'ph_range': (min(phs), max(phs)) if phs else None,
+            'optimal_ph': sum(phs) / len(phs) if phs else None,
+            'optimal_temperature': sum(temperatures) / len(temperatures) if temperatures else None,
+            'temperature_range': (min(temperatures), max(temperatures)) if temperatures else None,
+            'stability_ph': ph_stabilities[0] if ph_stabilities else None,
+            'temperature_stability': temp_stabilities[0] if temp_stabilities else None
+        }
+
+        return params
+
+    except Exception as e:
+        print(f"Error getting environmental parameters for {ec_number}: {e}")
+        return {'ec_number': ec_number, 'error': str(e)}
+
+
+def get_cofactor_requirements(ec_number: str) -> List[Dict[str, Any]]:
+    """Get cofactor requirements for an enzyme from reaction data."""
+    validate_dependencies()
+
+    cofactors = []
+
+    try:
+        reactions = get_reactions(ec_number)
+        time.sleep(0.5)  # Rate limiting
+
+        for entry in reactions:
+            parsed = parse_reaction_entry(entry)
+            if parsed and 'reactants' in parsed:
+                # Look for common cofactors in reactants
+                common_cofactors = [
+                    'NAD+', 'NADH', 'NADP+', 'NADPH',
+                    'ATP', 'ADP', 'AMP',
+                    'FAD', 'FADH2',
+                    'CoA', 'acetyl-CoA',
+                    'pyridoxal phosphate', 'PLP',
+                    'biotin',
+                    'heme', 'iron-sulfur'
+                ]
+
+                for reactant in parsed['reactants']:
+                    for cofactor in common_cofactors:
+                        if cofactor.lower() in reactant.lower():
+                            cofactors.append({
+                                'name': cofactor,
+                                'full_name': reactant,
+                                'type': 'oxidoreductase' if 'NAD' in cofactor else 'other',
+                                'organism': parsed.get('organism', ''),
+                                'ec_number': ec_number
+                            })
+
+    except Exception as e:
+        print(f"Error getting cofactor requirements for {ec_number}: {e}")
+
+    # Remove duplicates
+    unique_cofactors = []
+    seen = set()
+    for cofactor in cofactors:
+        key = (cofactor['name'], cofactor['organism'])
+        if key not in seen:
+            seen.add(key)
+            unique_cofactors.append(cofactor)
+
+    return unique_cofactors
+
+
+def get_substrate_specificity(ec_number: str) -> List[Dict[str, Any]]:
+    """Get substrate specificity data for an enzyme."""
+    validate_dependencies()
+
+    specificity = []
+
+    try:
+        km_data = get_km_values(ec_number)
+        time.sleep(0.5)  # Rate limiting
+
+        substrate_data = {}
+
+        for entry in km_data:
+            parsed = parse_km_entry(entry)
+            if 'substrate' in parsed and 'km_value_numeric' in parsed:
+                substrate = parsed['substrate']
+                if substrate not in substrate_data:
+                    substrate_data[substrate] = {
+                        'name': substrate,
+                        'km_values': [],
+                        'organisms': set(),
+                        'vmax_values': [],  # If available
+                        'kcat_values': []   # If available
+                    }
+
+                substrate_data[substrate]['km_values'].append(parsed['km_value_numeric'])
+                if 'organism' in parsed:
+                    substrate_data[substrate]['organisms'].add(parsed['organism'])
+
+        # Calculate summary statistics
+        for substrate, data in substrate_data.items():
+            if data['km_values']:
+                specificity.append({
+                    'name': substrate,
+                    'km': sum(data['km_values']) / len(data['km_values']),
+                    'min_km': min(data['km_values']),
+                    'max_km': max(data['km_values']),
+                    'data_points': len(data['km_values']),
+                    'organisms': list(data['organisms']),
+                    'vmax': sum(data['vmax_values']) / len(data['vmax_values']) if data['vmax_values'] else None,
+                    'kcat': sum(data['kcat_values']) / len(data['kcat_values']) if data['kcat_values'] else None,
+                    'kcat_km_ratio': None  # Would need kcat data to calculate
+                })
+
+        # Sort by Km (lower is better affinity)
+        specificity.sort(key=lambda x: x['km'] if x['km'] else float('inf'))
+
+    except Exception as e:
+        print(f"Error getting substrate specificity for {ec_number}: {e}")
+
+    return specificity
+
+
+def compare_substrate_affinity(ec_number: str) -> List[Dict[str, Any]]:
+    """Compare substrate affinity for an enzyme."""
+    return get_substrate_specificity(ec_number)
+
+
+def get_inhibitors(ec_number: str) -> List[Dict[str, Any]]:
+    """Get inhibitor information for an enzyme (from commentary)."""
+    validate_dependencies()
+
+    inhibitors = []
+
+    try:
+        km_data = get_km_values(ec_number)
+        time.sleep(0.5)  # Rate limiting
+
+        for entry in km_data:
+            parsed = parse_km_entry(entry)
+            commentary = parsed.get('commentary', '').lower()
+
+            # Look for inhibitor keywords
+            inhibitor_keywords = ['inhibited', 'inhibition', 'blocked', 'prevented', 'reduced']
+            if any(keyword in commentary for keyword in inhibitor_keywords):
+                # Try to extract inhibitor names (this is approximate)
+                # Common inhibitors
+                common_inhibitors = [
+                    'iodoacetate', 'n-ethylmaleimide', 'p-chloromercuribenzoate',
+                    'heavy metals', 'mercury', 'copper', 'zinc',
+                    'cyanide', 'azide', 'carbon monoxide',
+                    'edta', 'egta'
+                ]
+
+                for inhibitor in common_inhibitors:
+                    if inhibitor in commentary:
+                        inhibitors.append({
+                            'name': inhibitor,
+                            'type': 'irreversible' if 'iodoacetate' in inhibitor or 'maleimide' in inhibitor else 'reversible',
+                            'organism': parsed.get('organism', ''),
+                            'ec_number': ec_number,
+                            'commentary': parsed.get('commentary', '')
+                        })
+
+    except Exception as e:
+        print(f"Error getting inhibitors for {ec_number}: {e}")
+
+    # Remove duplicates
+    unique_inhibitors = []
+    seen = set()
+    for inhibitor in inhibitors:
+        key = (inhibitor['name'], inhibitor['organism'])
+        if key not in seen:
+            seen.add(key)
+            unique_inhibitors.append(inhibitor)
+
+    return unique_inhibitors
+
+
+def get_activators(ec_number: str) -> List[Dict[str, Any]]:
+    """Get activator information for an enzyme (from commentary)."""
+    validate_dependencies()
+
+    activators = []
+
+    try:
+        km_data = get_km_values(ec_number)
+        time.sleep(0.5)  # Rate limiting
+
+        for entry in km_data:
+            parsed = parse_km_entry(entry)
+            commentary = parsed.get('commentary', '').lower()
+
+            # Look for activator keywords
+            activator_keywords = ['activated', 'stimulated', 'enhanced', 'increased']
+            if any(keyword in commentary for keyword in activator_keywords):
+                # Try to extract activator names (this is approximate)
+                common_activators = [
+                    'mg2+', 'mn2+', 'ca2+', 'zn2+',
+                    'k+', 'na+',
+                    'phosphate', 'pyrophosphate',
+                    'dithiothreitol', 'dtt',
+                    'β-mercaptoethanol'
+                ]
+
+                for activator in common_activators:
+                    if activator in commentary:
+                        activators.append({
+                            'name': activator,
+                            'type': 'metal ion' if '+' in activator else 'reducing agent' if 'dtt' in activator.lower() or 'mercapto' in activator.lower() else 'other',
+                            'mechanism': 'allosteric' if 'allosteric' in commentary else 'cofactor' else 'unknown',
+                            'organism': parsed.get('organism', ''),
+                            'ec_number': ec_number,
+                            'commentary': parsed.get('commentary', '')
+                        })
+
+    except Exception as e:
+        print(f"Error getting activators for {ec_number}: {e}")
+
+    # Remove duplicates
+    unique_activators = []
+    seen = set()
+    for activator in activators:
+        key = (activator['name'], activator['organism'])
+        if key not in seen:
+            seen.add(key)
+            unique_activators.append(activator)
+
+    return unique_activators
+
+
+def find_thermophilic_homologs(ec_number: str, min_temp: int = 50) -> List[Dict[str, Any]]:
+    """Find thermophilic homologs of an enzyme."""
+    validate_dependencies()
+
+    thermophilic = []
+
+    try:
+        organisms = get_organisms_for_enzyme(ec_number)
+
+        for organism in organisms:
+            # Check if organism might be thermophilic based on name
+            thermophilic_keywords = ['therm', 'hypertherm', 'pyro']
+            if any(keyword in organism.lower() for keyword in thermophilic_keywords):
+                # Get kinetic data to extract temperature information
+                km_data = get_km_values(ec_number, organism=organism)
+                time.sleep(0.2)  # Rate limiting
+
+                temperatures = []
+                kms = []
+
+                for entry in km_data:
+                    parsed = parse_km_entry(entry)
+                    if 'temperature' in parsed:
+                        temperatures.append(parsed['temperature'])
+                    if 'km_value_numeric' in parsed:
+                        kms.append(parsed['km_value_numeric'])
+
+                if temperatures and max(temperatures) >= min_temp:
+                    thermophilic.append({
+                        'organism': organism,
+                        'ec_number': ec_number,
+                        'optimal_temperature': max(temperatures),
+                        'temperature_range': (min(temperatures), max(temperatures)),
+                        'km': sum(kms) / len(kms) if kms else None,
+                        'data_points': len(km_data)
+                    })
+
+    except Exception as e:
+        print(f"Error finding thermophilic homologs for {ec_number}: {e}")
+
+    return thermophilic
+
+
+def find_ph_stable_variants(ec_number: str, min_ph: float = 8.0, max_ph: float = 6.0) -> List[Dict[str, Any]]:
+    """Find pH-stable variants of an enzyme."""
+    validate_dependencies()
+
+    ph_stable = []
+
+    try:
+        organisms = get_organisms_for_enzyme(ec_number)
+
+        for organism in organisms:
+            km_data = get_km_values(ec_number, organism=organism)
+            time.sleep(0.2)  # Rate limiting
+
+            phs = []
+            kms = []
+
+            for entry in km_data:
+                parsed = parse_km_entry(entry)
+                if 'ph' in parsed:
+                    phs.append(parsed['ph'])
+                if 'km_value_numeric' in parsed:
+                    kms.append(parsed['km_value_numeric'])
+
+            if phs:
+                ph_range = (min(phs), max(phs))
+                is_alkaline_stable = min_ph and ph_range[0] >= min_ph
+                is_acid_stable = max_ph and ph_range[1] <= max_ph
+
+                if is_alkaline_stable or is_acid_stable:
+                    ph_stable.append({
+                        'organism': organism,
+                        'ec_number': ec_number,
+                        'ph_range': ph_range,
+                        'optimal_ph': sum(phs) / len(phs),
+                        'km': sum(kms) / len(kms) if kms else None,
+                        'stability_type': 'alkaline' if is_alkaline_stable else 'acidic',
+                        'data_points': len(km_data)
+                    })
+
+    except Exception as e:
+        print(f"Error finding pH-stable variants for {ec_number}: {e}")
+
+    return ph_stable
+
+
+def get_modeling_parameters(ec_number: str, substrate: str = None) -> Dict[str, Any]:
+    """Get parameters suitable for kinetic modeling."""
+    validate_dependencies()
+
+    try:
+        if substrate:
+            km_data = get_km_values(ec_number, substrate=substrate)
+        else:
+            km_data = get_km_values(ec_number)
+
+        time.sleep(0.5)  # Rate limiting
+
+        if not km_data:
+            return {'ec_number': ec_number, 'error': 'No kinetic data found'}
+
+        # Extract modeling parameters
+        kms = []
+        phs = []
+        temperatures = []
+        v_max_values = []
+        kcat_values = []
+
+        for entry in km_data:
+            parsed = parse_km_entry(entry)
+
+            if 'km_value_numeric' in parsed:
+                kms.append(parsed['km_value_numeric'])
+            if 'ph' in parsed:
+                phs.append(parsed['ph'])
+            if 'temperature' in parsed:
+                temperatures.append(parsed['temperature'])
+
+            # Look for Vmax and kcat in commentary (rare in BRENDA)
+            commentary = parsed.get('commentary', '').lower()
+            vmax_match = re.search(r'vmax\s*=\s*([\d.]+)', commentary)
+            if vmax_match:
+                v_max_values.append(float(vmax_match.group(1)))
+
+            kcat_match = re.search(r'kcat\s*=\s*([\d.]+)', commentary)
+            if kcat_match:
+                kcat_values.append(float(kcat_match.group(1)))
+
+        modeling_data = {
+            'ec_number': ec_number,
+            'substrate': substrate if substrate else 'various',
+            'km': sum(kms) / len(kms) if kms else None,
+            'km_std': (sum((x - sum(kms)/len(kms))**2 for x in kms) / len(kms))**0.5 if kms else None,
+            'vmax': sum(v_max_values) / len(v_max_values) if v_max_values else None,
+            'kcat': sum(kcat_values) / len(kcat_values) if kcat_values else None,
+            'optimal_ph': sum(phs) / len(phs) if phs else None,
+            'optimal_temperature': sum(temperatures) / len(temperatures) if temperatures else None,
+            'data_points': len(km_data),
+            'temperature': sum(temperatures) / len(temperatures) if temperatures else 25.0,  # Default to 25°C
+            'ph': sum(phs) / len(phs) if phs else 7.0,  # Default to pH 7.0
+            'enzyme_conc': 1.0,  # Default enzyme concentration (μM)
+            'substrate_conc': None,  # Would be set by user
+        }
+
+        return modeling_data
+
+    except Exception as e:
+        return {'ec_number': ec_number, 'error': str(e)}
+
+
+def export_kinetic_data(ec_number: str, format: str = 'csv', filename: str = None) -> str:
+    """Export kinetic data to file."""
+    validate_dependencies()
+
+    if not filename:
+        filename = f"brenda_kinetic_data_{ec_number.replace('.', '_')}.{format}"
+
+    try:
+        # Get all kinetic data
+        km_data = get_km_values(ec_number)
+        time.sleep(0.5)  # Rate limiting
+
+        if not km_data:
+            print(f"No kinetic data found for EC {ec_number}")
+            return filename
+
+        # Parse all entries
+        parsed_data = []
+        for entry in km_data:
+            parsed = parse_km_entry(entry)
+            if parsed:
+                parsed_data.append(parsed)
+
+        # Export based on format
+        if format.lower() == 'csv':
+            if parsed_data:
+                df = pd.DataFrame(parsed_data)
+                df.to_csv(filename, index=False)
+            else:
+                with open(filename, 'w', newline='') as f:
+                    f.write('No data found')
+
+        elif format.lower() == 'json':
+            with open(filename, 'w') as f:
+                json.dump(parsed_data, f, indent=2, default=str)
+
+        elif format.lower() == 'excel':
+            if parsed_data and PANDAS_AVAILABLE:
+                df = pd.DataFrame(parsed_data)
+                df.to_excel(filename, index=False)
+            else:
+                print("pandas required for Excel export")
+                return filename
+
+        print(f"Exported {len(parsed_data)} entries to {filename}")
+        return filename
+
+    except Exception as e:
+        print(f"Error exporting data: {e}")
+        return filename
+
+
+def search_by_pattern(pattern: str, limit: int = 50) -> List[Dict[str, Any]]:
+    """Search enzymes using a reaction pattern or keyword."""
+    validate_dependencies()
+
+    enzymes = []
+
+    try:
+        # Search reactions containing the pattern
+        reactions = get_reactions("*", reaction=f"*{pattern}*")
+        time.sleep(0.5)  # Rate limiting
+
+        for entry in reactions[:limit]:
+            parsed = parse_reaction_entry(entry)
+            if parsed:
+                enzymes.append({
+                    'ec_number': parsed.get('ecNumber', ''),
+                    'organism': parsed.get('organism', ''),
+                    'reaction': parsed.get('reaction', ''),
+                    'reactants': parsed.get('reactants', []),
+                    'products': parsed.get('products', []),
+                    'commentary': parsed.get('commentary', '')
+                })
+
+    except Exception as e:
+        print(f"Error searching by pattern '{pattern}': {e}")
+
+    return enzymes
+
+
+if __name__ == "__main__":
+    # Example usage
+    print("BRENDA Database Query Examples")
+    print("=" * 40)
+
+    try:
+        # Example 1: Search enzymes by substrate
+        print("\n1. Searching enzymes for 'glucose':")
+        enzymes = search_enzymes_by_substrate("glucose", limit=5)
+        for enzyme in enzymes:
+            print(f"  EC {enzyme['ec_number']}: {enzyme['organism']}")
+            print(f"    Km: {enzyme['km_value']}")
+
+        # Example 2: Compare across organisms
+        print("\n2. Comparing alcohol dehydrogenase (1.1.1.1) across organisms:")
+        organisms = ["Escherichia coli", "Saccharomyces cerevisiae", "Homo sapiens"]
+        comparison = compare_across_organisms("1.1.1.1", organisms)
+        for comp in comparison:
+            if comp.get('data_points', 0) > 0:
+                print(f"  {comp['organism']}:")
+                print(f"    Avg Km: {comp.get('average_km', 'N/A')}")
+                print(f"    Optimal pH: {comp.get('optimal_ph', 'N/A')}")
+
+        # Example 3: Get environmental parameters
+        print("\n3. Environmental parameters for 1.1.1.1:")
+        params = get_environmental_parameters("1.1.1.1")
+        if params.get('data_points', 0) > 0:
+            print(f"  pH range: {params.get('ph_range', 'N/A')}")
+            print(f"  Temperature range: {params.get('temperature_range', 'N/A')}")
+
+    except Exception as e:
+        print(f"Example failed: {e}")