Lesson 4.8. Antibiotic Production of Fungi

Penicillin

• one of the most important discoveries regarding the use of fungi by Sir Alexander Fleming (1929)

• capable of killing Gram-positive bacteria

Penicillium notatum

The first Penicillin was a _______________ isolate

beta-lactam

Penicillin is the first member of __________ class of antibiotics which inhibits peptidoglycan synthesis in bacteria

Penicillium chrysogenum

Today,_________________ is a superior producer of Penicillin

Penicillin V

penicillin fermentation yields penicillin F, G and V:

1. ________________ can be used directly, delivered intravenously

2. ________________ is modified by penicillin acylase to give a variety of semisynthetic penicillins

1 = ?

Penicillin G

penicillin fermentation yields penicillin F, G and V:

1. ________________ can be used directly, delivered intravenously

2. ________________ is modified by penicillin acylase to give a variety of semisynthetic penicillins

2 = ?

antibiotics

secondary metabolites produced during the stationary phase and is linked to sporulation

catabolite repression

Inhibitions of antibiotic production

• microorganisms to adapt quickly to a preferred carbon and energy source first (glucose)

• avoided by using low levels of glucose in the fermentation medium or obtain a mutant that is not catabolite repressed

high levels of nitrogen or phosphate

Inhibitions of antibiotic production

• chemical content of the medium must be monitored

Feedback Inhibition

Inhibitions of antibiotic production

• antibiotic buildup will retard production or kills the cell

• introduce low levels of amphotericin B to decrease intracellular antibiotic levels and a concomitant increase in production

mutagenesis and selection

Optimization of antibiotic production

1. random _______________________

2. ______________________________ with good secretors

3. _______________ – a chelating agent is introduced into the fermentation to complex all the metal ions present and has beneficial effect on antibiotic production

4. _______________ – to express the genes for antibiotic production in other species which has the possibility of producing hybrid antibiotics with novel targets

1 = ?

fuse or mate high-producing strains

Optimization of antibiotic production

1. random _______________________

2. ______________________________ with good secretors

3. _______________ – a chelating agent is introduced into the fermentation to complex all the metal ions present and has beneficial effect on antibiotic production

4. _______________ – to express the genes for antibiotic production in other species which has the possibility of producing hybrid antibiotics with novel targets

2 = ?

rational selection

Optimization of antibiotic production

1. random _______________________

2. ______________________________ with good secretors

3. _______________ – a chelating agent is introduced into the fermentation to complex all the metal ions present and has beneficial effect on antibiotic production

4. _______________ – to express the genes for antibiotic production in other species which has the possibility of producing hybrid antibiotics with novel targets

3 = ?

genetic manipulation

Optimization of antibiotic production

1. random _______________________

2. ______________________________ with good secretors

3. _______________ – a chelating agent is introduced into the fermentation to complex all the metal ions present and has beneficial effect on antibiotic production

4. _______________ – to express the genes for antibiotic production in other species which has the possibility of producing hybrid antibiotics with novel targets

4 = ?