Enzyme promiscuity refers to an enzyme's ability to catalyze secondary reactions beyond its main physiological reaction. While enzymes are highly specific catalysts, they can often perform side reactions in addition to their primary activity. These promiscuous activities are usually less efficient than the main reaction, but can occasionally confer an evolutionary advantage and lead to the development of new enzyme functions. Promiscuous enzyme activities are being exploited in applications such as pharmaceutical production and the synthesis of food and flavor compounds.

1. Promiscuous Enzymes
Presented by- Vikrant Rana

2. What is Enzyme Promiscuity?
“The term ‘promiscuous’ is used to describe enzymes that catalyze more than
one reaction”
“Enzyme promiscuity is an ability to catalyze secondary reactions that are
physiologically irrelevant”

3. • Enzyme promiscuity is the ability of an enzymes to catalyse a
fortuitous side reaction in addition to its main reaction.
Although enzymes are remarkably specific catalysts, they can
often perform side reactions in addition to their main, native
catalytic activity.
• These promiscuous activities are usually slow relative to the
main activity and are under neutral selection. Despite
ordinarily being physiologically irrelevant, under new selective
pressures these activities may confer a fitness benefit
therefore prompting the evolution of the formerly
promiscuous activity to become the new main activity.

4. Physiological function:
Lactonase: Hydrolysis of oxidized
lipids
Secondary Function: OP hydrolase
Physiological function:
Lactonase: Vitamin C biosynthesis
Secondary Function: OP hydrolase

7. • The biocatalysts normally do not require high temperature or
other conditions which involve high consumption of energy.
The biocatalysts are believed to be fairly specific, which would
mean less number of side reactions. Side reactions lead to
side products which lower the atom economy of the
reactions. These side reactions hence lower the yield of the
desired product (making the catalysis less efficient) and
necessitate complicated down.
• The results of these studies show that enzymes often do not
accept just a single substrate, but instead accept a range of
substrates
Mechanism:

8. • In a growing number of enzymes a feature termed catalytic
promiscuity has been identified, which can be defined as the
capability of an enzyme to catalyze a chemically, and often
mechanistically, distinct transformation in addition to its
biologically relevant one.
• Already in the 1970s, it was postulated that if a catalytically
promiscuous activity could provide a selective advantage for
the host organism, such a promiscuous activity could be the
starting point for the evolution of a new enzyme.

9. • A low-level promiscuous activity can be amplified by accumulation
of mutations, preceded or followed by gene duplication. The
promiscuous activity of the parent enzyme then becomes the
primary activity of the newly evolved enzyme. This concept is
nowadays widely accepted and worked out in more detail by a
number of key studies on enzyme promiscuity.
• Second, the characterization of catalytically promiscuous activities
of enzymes can aid in the identification of active site residues as
catalytically important. Moreover, insight can be gained into the
mechanistic roles of active site residues. Often it is found that the
same set of catalytic residues is involved in both the enzyme’s
native and promiscuous activity, but that these residues fulfill a
different mechanistic role.

10. • Third, the presence of catalytic promiscuity shows the
chemical versatility of an enzyme’s active site. In fact, catalytic
promiscuity might even be predicted based on knowledge of
the chemical and mechanistic properties of active site
residues. Here lie formidable challenges and possibilities: the
use of mechanistic reasoning to discover new promiscuous
activities in existing enzymes, which could be exploited to
generate novel biocatalysts.

11. Source: www.researchgate.net

12. Degree of promiscuity
• Enzymes are generally in a state that is not only a compromise
between stability and catalytic efficiency, but also for
specificity and evolvability, the latter two dictating whether an
enzyme is a generalist (highly evolvable due to large
promiscuity, but low main activity) or a specialist (high main
activity, poorly evolvable due to low promiscuity). Examples of
these are enzymes for primary and secondary metabolism in
plants.

13. Types of enzyme promiscuity:

14. • Enzyme condition promiscuity: Shown by enzymes with
catalytic activity in various reaction conditions different from
their natural ones, such as anhydrous media, extreme
temperature and pH.
• Enzyme substrate promiscuity: Shown by enzymes with
relaxed or broad substrate specificity.
• Enzyme catalytic promiscuity: Shown by enzymes catalysing
distinctly different chemical transformations with different
transition states. It can be
1. Accidental- a side reaction catalysed by wild-type enzyme
2. Induced- a new reaction established by one or several
mutations

15. Source: www.researchgate.net

16. Application in pharmaceutical industry
• Dr. Reddy’s Laboratory in production of mintop 10
solution which is a bioactive serum.
• In production of Biocon’s immunosuppressant and
statins
• Insulins and analogs
• In food products, used in USA by Dr. Trust in
production of digestive enzyme.
• Also used in production of some flavour compounds.

17. Conclusion
• Enzyme promiscuity is a property shown by many enzymes,
nowadays exploited in applied enzymology .It is classified in to
conditional , substrate and catalytic which results into many
industrial applications.
• Over last few years, it have been observed that other classes
of enzymes(hydrolases, oxidoreductases, transferases etc. are
being capable of showing catalytic promiscuity.

18. References:
• Gupta MN, Raghava S: Relevance of chemistry to white
biotechnology. Chem Cent J 2007, 1:17
• Ulber R, Sell D: White Biotechnology. Berlin: Springer-Verlag;
2007
• Kazlauskas RJ: Enhancing catalytic promiscuity for biocatalysis.
Curr Opin Chem Biol 2005, 9:195–201
• Khersonsky O, Tawfik DS: Enzyme promiscuity: a mechanistic
and evolutionary perspective. Annu Rev Biochem 2010,
79:471–505