Bioconversions

Nisa Rachmania Mubarik

Mikrob dan Potensinya

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Bioconversions or Microbial Transformation
The ability of microbes to chemically modify a wide
variety of organic compounds. The substrate may be
metabolized or take place without energy gain
(cometabolism).
Bioconversion is often preferable:
1. Substrate specificity : only one specific reaction step is
normally catalyzed by an enzyme
2. Sitespecificity (Regiospecificity): only one type
functional group may be affected
3. Stereospecificity: only one specific enantiomer is
converted. The reaction product is normally optically
active.
4. Reaction conditions: enzymatic reactions do not cause
destructionof sensitive substrates, due to the mild
condiotions of conversion.
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 Types of Bioconversion Reactions
1. Oxidations
2. Reductions
3. Hydrolytic Reactions
4. Condensations

Procedures for Biotransformation

1. Culture (spores, growing cultures, resting cells, cell-free enzyme extracts,
immobilized cells), enzymes or immobilized enzymes
2. Suitable medium
3. Conversion time is related to the type of reaction, the substrate
concentration, and the microorganism used
4. Applications of bioconversions: industrial, more cost effective processes,
optimized for specific proceses.

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 Transformation of Antibiotics
The objective is the development of modified antibiotics with improved
effectiveness, reduced toxicity, wider antimicrobial spectrum, improved
oral absorption, decreased development of resistance, or lower allergic
effects.
Types of antibiotic transformation:
1. Indirect transformation. The addition of inhibitors or modified precursors
to the medium may result in the synthsis of altered antibiotics via
controlled biosynthesis. E.g. Streptomyces parvulus produces two new
actinomycins which proline is replaced by this proline analog.
2. Direct transformation. Acylation reactions, deacylation reactions,
phosphorylation, hydrolysis reaction, and hydroxylation.
E.g. Hydrolysis reactions → splitting of the lactone ring of -lactam
antibiotics (penicillins & cephalosporins) by -lactamase, leading to
inactivation of the antibiotics.

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The photo (courtesy of Merck & Co., Inc.)
shows how the growth of bacteria on the
agar in a culture dish has been inhibited by
the three circular colonies of the fungus
Penicillium notatum. The antibiotic
penicillin, diffusing outward from the
colonies, is responsible for this effect. Today,
penicillin is made from cultures of
Penicillium chrysogenum that has been
specially adapted for high yields.
http://users.rcn.com/jkimball.ma.ultranet/Biol
ogyPages/A/Antibiotics.html
The beta-lactams get their name
from the characteristic ring
structure — shown here in blue
— that they all share. (The green
arrow shows the bond that is
broken by the beta-lactamases
that are synthesized by many
penicillin-resistant bacteria.)
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 Transformation of Pesticides
Microbial transformation is of interest not for the production of new active
agents, but for the greatest possible detoxification of the environment.

Removal of pesticides can be accomplished through various mechanisms:

1. Pesticides as carbon sources. E.g. The herbicide Dalapon, a
chlorinated fatty acid, which is converted by Arthrobacter sp. into
pyruvate after oxidative dehalogenation.

Dalapon

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 Dalapon
Status:BSI
IUPAC:2,2-dichloropropionic acidCAS:2,2-dichloropropanoic acid
Reg. No.:75-99-0
Formula:C3H4Cl2O2
Activity:herbicides (halogenated aliphatic herbicides)
Notes:There is no ISO common name for this substance; the name
“dalapon” is approved by the British Standards Institution and the Weed
Science Society of America.
When this substance is used as an ester or a salt, its identity should be
stated, for example dalapon-calcium [53606-78-3], dalapon-magnesium
[29110-22-3], dalapon-sodium [127-20-8].
The 2-(2,4,5-trichlorophenoxy)ethyl ester has its own ISO common name,
erbon.

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 2. Cometabolism. Microorganisms do not obtain energy from the
transformation reaction and require another substrate for growth.
Dehalogenation or oxidative dehalogenation reactions which make
pesticide molecules accessible for further breakdown.
E.g. Reductive dehalogenation DDT (dichlorodiphenyl
trichloroethane) → TDE by Aerobacter aerogenes
Dehydrohalogenation DDT → DDE by Trichoderma viride

Synonyms for DDT: 1,1,1-trichloro-2,2-bis(p-chlorophenyl)-ethane; Chlorophenothane

Synonyms for TDE: 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethane;
Tetrachlorodiphenylethane; Rhothane;
Synonyms for p,p'-DDE:1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene; p,p'-
dichlorodiphenyldichloroethylene
Bioassays of technical-grade DDT, TDE, and p,p'-DDE for possible carcinogenicity were
conducted using Osborne-Mendel rats and B6C3F1 mice
http://ntp.niehs.nih.gov/index.cfm?objectid=0704C8A4-F52A-BE78-5C81C16C5C1F14C9
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 DDT has an extremely low volatility and may be the least soluble chemical
known, which makes it extremely persistent in soils and aquatic sediments. It
has relatively low acute mammalian toxicity and is toxic to a wide range of
insects. It kills insects by affecting the transmission of nerve impulses,
probably by influencing the delicate balance of sodium and potassium within
the neuron.

A comparison of a normal Peregrine falcon eggshell and one thinned byexposure

to the pesticide DDT. (©Galen Rowell/Corbis. Reproduced by permission.)
http://www.pollutionissues.com/Co-Ea/DDT-Dichlorodiphenyl-Trichloroethane.html

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3. Conjugate formation. Linkage of pesticides or decomposition products
with naturally compounds such as amino acids or carbohydrates
results only in a temporary detoxfication. E.g. Conversion of a
dithiocarbamate fungicide by E. coli, S. cerevisiae, A. niger, and
Hansenula anomale.
Thiocarbamates are
mainly used in agriculture
as insect- icides,
herbicides, and
fungicides. Additional
uses are as biocides for
industrial or other
commercial applications,
and in household
products. Some are used
for vector control in public
health.
http://www.intox.org/data
bank/documents/chemica
l/thiocarb/ehc76.htm
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 Biotransformation of L-ascorbic acid (Vitamin C)
D-Glukosa → D-sorbitol L-sorbose → 2-keto-L-
sorbitol dehydrogenase
Acetobacter suboxydans
A. xylinum
gulonic acid →sodium salt/2-keto-L-gulonic acid→L-ascorbic acid

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