scholarly journals Modeling of Clavulanic Acid Production from Streptomyces clavuligerus using a Continuous Operation Mode

2021 ◽  
Vol 2049 (1) ◽  
pp. 012073
Author(s):  
L Ariza ◽  
J Rubio ◽  
V Moreno ◽  
L Niño ◽  
G Gelves
Keyword(s):  
Clavulanic Acid ◽  
Acid Production ◽  
Large Scale ◽  
Antibiotic Production ◽  
Simulated Data ◽  
Streptomyces Clavuligerus ◽  
Production Optimization ◽  
Computational Techniques ◽  
Batch Mode ◽  
Starting Point

Abstract Clavulanic acid is a β-lactam inhibitor produced by fermentation with Streptomyces clavuligerus cells, and it is usually used to prevent resistance to certain antibiotics. However, CA production is limited at the bioreactor level due to its low performance. The latter generates expensive processes and challenging to operate on a large scale. In this research, a mathematical model is proposed to simulate the clavulanic acid production from an operation strategy based on continuous mode. The preceding, to identify trends allowing to improve the productivity of the mentioned metabolite. Results are compared to the traditional operating batch mode. According to the results found, the final concentration of the β-lactam inhibitor could be increased by up to 60% regarding the simulated data in batch mode. Results obtained demonstrate the importance of computational techniques in bioprocess engineering since bioprocess simulation focuses on identifying critical operating parameters as a starting point in antibiotic production optimization.

scholarly journals Glycerol Utilization Gene Cluster in Streptomyces clavuligerus

2009 ◽  
Vol 75 (9) ◽  
pp. 2991-2995 ◽  
Author(s):  
Sonia Baños ◽  
Rosario Pérez-Redondo ◽  
Bert Koekman ◽  
Paloma Liras
Keyword(s):  
Clavulanic Acid ◽  
Gene Cluster ◽  
Acid Production ◽  
Type Strain ◽  
Wild Type Strain ◽  
Streptomyces Clavuligerus ◽  
Wild Type ◽  
Glycerol Utilization ◽  
In The Wild

ABSTRACT The Streptomyces clavuligerus ATCC 27064 glycerol cluster gylR-glpF1K1D1 is induced by glycerol but is not affected by glucose. S. clavuligerus growth and clavulanic acid production are stimulated by glycerol, but this does not occur in a glpK1-deleted mutant. Amplification of glpK1D1 results in transformants yielding larger amounts of clavulanic acid in the wild-type strain and in overproducer S. clavuligerus Gap15-7-30 or S. clavuligerus ΔrelA strains.

scholarly journals Clavulanic acid production by the MMS 150 mutant obtained from wild type Streptomyces clavuligerus ATCC 27064

2013 ◽  
Vol 44 (4) ◽  
pp. 1049-1057 ◽  
Author(s):  
Eliton da Silva Vasconcelos ◽  
Vanderlei Aparecido de Lima ◽  
Leandro Seiji Goto ◽  
Isara Lourdes Cruz-Hernández ◽  
Carlos Osamu Hokka
Keyword(s):  
Clavulanic Acid ◽  
Acid Production ◽  
Streptomyces Clavuligerus ◽  
Wild Type

scholarly journals Five Additional Genes Are Involved in Clavulanic Acid Biosynthesis in Streptomyces clavuligerus

2004 ◽  
Vol 48 (1) ◽  
pp. 192-202 ◽  
Author(s):  
S. E. Jensen ◽  
A. S. Paradkar ◽  
R. H. Mosher ◽  
C. Anders ◽  
P. H. Beatty ◽  
...  
Keyword(s):  
Cell Wall ◽  
Clavulanic Acid ◽  
Gene Cluster ◽  
Acid Production ◽  
Streptomyces Clavuligerus ◽  
Open Reading Frames ◽  
Acid Biosynthesis ◽  
Penicillin Binding Proteins ◽  
Total Absence ◽  
Reading Frames

ABSTRACT An approximately 12.5-kbp region of DNA sequence from beyond the end of the previously described clavulanic acid gene cluster was analyzed and found to encode nine possible open reading frames (ORFs). Involvement of these ORFs in clavulanic acid biosynthesis was assessed by creating mutants with defects in each of the ORFs. orf12 and orf14 had been previously reported to be involved in clavulanic acid biosynthesis. Now five additional ORFs are shown to play a role, since their mutation results in a significant decrease or total absence of clavulanic acid production. Most of these newly described ORFs encode proteins with little similarity to others in the databases, and so their roles in clavulanic acid biosynthesis are unclear. Mutation of two of the ORFs, orf15 and orf16, results in the accumulation of a new metabolite, N-acetylglycylclavaminic acid, in place of clavulanic acid. orf18 and orf19 encode apparent penicillin binding proteins, and while mutations in these genes have minimal effects on clavulanic acid production, their normal roles as cell wall biosynthetic enzymes and as targets for β-lactam antibiotics, together with their clustered location, suggest that they are part of the clavulanic acid gene cluster.

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