 |
| |
|
|
Q
|
What is 7-ADCA? |
|
A
|
7-ADCA is 7-amino deacetoxycephalosporanic
acid for short. It is the intermediates for the ready synthesis
if cephalosporins cefalexcin, cefadroxil and cefradine. |
|
|
|
|
Q
|
What is the market
value of 7-ADCA? |
|
A
|
The requirement of 7-ADCA was 2,270
tonnes in 1997, and it is estimated that the requirement will
be up to 2,800 tonnes in 2010. The market price of 7-ADCA so
far is around $65/Kg, which means that the 7-ADCA business is
ranging from $130 to 150 millions. |
|
|
|
|
Q
|
Your company is executing
the program "Development of a bioprocess for preparation
of 7-ASDCA" partially supported
by MOEA. What is the significance of this program? |
|
A
|
The method currently used in industry
to prepare 7-ADCA is to chemically expand the 5-membered ring
of penicillin G to the 6-membered ring of cephalosporin G, then
the latter is subjected to side-chain removal catalyzed by penicillin
G acylase. It has been a great effort to replace this chemical
process with enzymatic reaction because of its high impact to
the envirement and high ratio of the cost. In this program,
we are going to exploit the enzyme expandase in the ring expansion
reaction, which has been studied for more than 20 years in other
companies and there was no great success obtained. Obviously,
if we can make it, it is not only impotant to us, but also to
all the companies in this field. |
|
|
|
|
Q
|
What is the expandase? |
|
A
|
Expandase is a natural enzyme existed
in the microorganisms which produce cephalosporins. Its main
function is to convert the 5-membered ring containing compound
penicillin N to the 6-membered ring containing compound deacetoxycephalosporanic
acid (DAOC). |
|
|
|
|
Q
|
Why it takes a long
time to replace the chemical expasion reaction with the expandase? |
|
A
|
Because the natural existed expandases
only have a high activity to penicillin N, but low to the commercially
available penicillin G. Acturally, the researchers even thought
that the expandases did not have any activity toward penicillinjG
until 1995. |
|
|
|
|
Q
|
Since the expandase
has a low activity to penicillin G, what is your approach to
solve this problem? |
|
A
|
Because the DNA sequence of the expandase
and its crystal structure have been unveiled recently, our strategy
is to clone the expandase gene first, then to make a random
mutation on this gene by error prone PCR. So, the key point
is how to select the mutated exzyme with high activity to penicillin
G. Do we already develop the sreening method? The answer is
yes. And we even got some high activity mutants, and the patent
is filing. |
| |
|
 |
| |
|
|
Q
|
What is bioconversion
? |
|
A
|
By clarifying the native biosynthetic
ability of a microorganism in terms of genes and enzymes, we
can genetically modify a microorganism to enable the microorganism
modifying chemical structure of a substrate, so that the microorganism
can produce useful target compound from natural or nonnatural
substrate. |
| |
|
 |
| |
|
|
Q
|
What is ACE Inhibitors? |
|
A
|
ACE inhibitors(angiotensin-converting
enzyme inhibitors) prevent certain enzymes in the body from
constricting blood vessels. This helps to lower blood pressure
and makes the heart beat stronger. This medication is used to
treat hypertension (high blood pressure) and heart failure. |
| |
|
|
Q
|
What is R-HPBA? |
|
A
|
Chiral building block used as a versatile
precursor for the synthesis of ACE-inhibitors. |
