Steroid transformation- Degradation of steroid nucleus

 Degradation of steroid nucleus

•      Growing demand for steroids – shortage of steroid precursors for bioconversion (eg., diosgenin)

•      Intensive studies on the use of low cost sterols of animal (cholesterol)/plant origin (sitosterol) (stigmasterol)

•      Complete breakdown of cholesterol is common with formation of CO₂ and H₂O

•      Side chain degradation of steroids - Selective removal of the aliphatic side chain without further breakdown of the steroidal nucleus

(1)      The breakdown of the side chain to yield C-17 keto steroids can be done by several organisms as given below. (Nocardia species)

•      Similar to β-oxidation of fatty acids

In another approach,

(2)     From cholesterol by opening of ring B,  the breakdown product 3-hydroxy-9,10-secoandrostatriene-9,17-dione produced

•     In the pathway, there is the  production of two useful intermediates – Androstenedione and androstadiendione

•      After androstadiendione,  9 α- hydroxy androstadiendione and 3-hydroxy-9,10-secoandrostatriene-9,17-dione is formed by C- (1(2)- dehydrogenation and 9 α- hydroxylation.  Thus, C- (1(2)- dehydrogenation and 9 α- hydroxylation are mandatory for complete breakdown of steroid ring

                      

•      In order to modify steroid nucleus without breaking of any rings, we can selectively block attack on the rings.

•  Thus we can obtain the two useful intermediates – Androstendione and androstadiendione

•      The breakdown of steroid nucleus is prevented by

•      chemical modification of the substrate

•      Use of inhibitors which prevent C- (1(2)- dehydrogenation and 9 α- hydroxylation (compounds which chelate Fe2+ or Cu2+/compounds which block sulfhydryl functions- Ni2+, Co2+, Pb2+)

•   Mutants with inactive C- (1(2)- dehydrogenase and 9 α- hydroxylase eg., Mycobacterium mutants isolated

ADVANTAGES

•      The ability of microorganisms, e.g., bacteria, to produce large amounts of biomass and a great variety of different enzymes in a short time.

•      The chemo-, regio-, and enantioselectivity of enzymes

•      Microorganisms have great potential for inducing new or novel enzyme systems capable of converting foreign substrates.

•      Microorganisms are capable of producing unique enzymes which are stable toward heat, alkali and acid.

•      A combination of microbial transformation and chemical transformations (chemo-enzymatic synthesis) can be exploited for partial, as well as the total synthesis of the organic compounds

DISADVANTAGES

•      If the substrate is toxic, it can kill the microorganisms. Hence no transformation will be observed.

•      Alternatively, if the micro-organisms use the substrate as an energy source (carbon source food), no transformed or untransformed material will be recovered.

•      Very low chemical yields are obtained due to the involvement of a complex biological system

•      Many of the ground rules for applying biotransformation are not yet well understood or well-defined.

•      Many chemical reactions have no equivalent biotransformation and vice- versa