Biotransformation of Steroids and Alkaloids

Overview of Steroids

• Steroids are organic compounds derived from alcohols, characterized by a tetracyclic ring system with 17 carbon atoms.
• The base skeletons are known as cyclopentanoperhydrophenanthrenes, including structures like gonane and estrane.
• Hydroxylated steroids, or sterols, have an OH group typically substituted at position C3 and include crucial compounds such as cholesterol, bile acids, sex hormones, and corticosteroids.

Biological Functions

• Steroids perform critical roles in biological systems:
  • Hormonal activity from androstane, pregnane, and estrane derivatives.
  • Bile acids aid in fat digestion and absorption.
  • Cardiotonic aglycones are utilized in heart disease treatment.
• Sterols maintain cell membrane integrity and serve as precursors for bile acids and steroid hormones.

Structure and Activity Correlation

• Physiological activity is influenced by:
  • Structure and orientation of functional groups within the tetracyclic structure.
  • Specific positions, such as:
    • C-11β – essential for anti-inflammatory effects.
    • C-17β – defines androgenic properties.
    • Aromatization of ring A – confers estrogenic effects.
    • Corticosteroids feature a 3-keto-4-ene group and a pregnane side chain at C-17.

Microbiological Transformations

• The introduction of hydroxyl groups through biohydroxylation is a key step in synthesizing physiologically active steroids.
• Microbiological transformations are effective for steroid bioconversion, often achieving what is challenging with conventional methods.
• Notable historical developments:
  • In 1950, cortisol and progesterone transformations using Rhizopus species marked a significant advance in steroid synthesis.

Historical Context in Steroid Manufacture

• The first microbial steroid transformation occurred in 1937, producing testosterone from dehydroepiandrosterone via Corynebacterium sp.
• The curative effects of cortisone on rheumatoid arthritis highlighted the need for efficient steroid manufacturing methods.
• Traditional methods were lengthy, such as producing cortisone through a laborious 32-step process from deoxycholic acid.

Types of Microbial Transformations

• Common transformation reactions include:
  • Hydroxylation, dehydrogenation, reduction, side chain degradation, lactone formation, aromatization, isomerization, and hydrolysis.
• Both steroid hormones and non-hormonal steroids like bile acids and alkaloids have been transformed.

Fermentation Conditions

• Transformation media generally consist of mineral salts and carbon sources (glucose, dextrin, glycerol).
• Non-water-soluble steroids require a water-miscible lipid solvent like acetone or ethanol to allow microbial action.
• Non-ionic surfactants such as Tween 80 are added to reduce surface tension and enhance steroid availability.

Microorganisms Involved

• Various fungi and bacteria are utilized for steroid transformations, including:
  • Fungi: Rhizopus nigricans, Curvularia lunata, Fusarium spp.
  • Bacteria: Mycobacterium spp., Corynebacterium simplex, Streptomyces spp.
• Transformations can be initiated at different growth stages of the microorganisms, and can involve resting or stationary cultures.

Techniques and Innovations

• The introduction of immobilized cells represents a modern advancement in steroid transformations.
• Specific techniques allow for targeted modifications to the steroid skeleton, facilitating the creation of new drug intermediates.

Explore the complex biotransformation processes of steroids and alkaloids. This quiz delves into the chemical structure, functions, and significance of these organic compounds in various biological systems. Test your knowledge on their hydroxylation and distribution in nature.