Application of Acid and Cold Stresses to Enhance the Production of Clavulanic Acid by Streptomyces clavuligerus

Autor(es)

Rodrigues, K. C. S. ^[1] ; Costa, C. L. L. ^[1] ; Badino, A. C. ^[1] ; Pedrolli, D. B. ^[2] ; Pereira, J. F. B. ^[2] ; Cerri, M. O. ^[2]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Carlos, Grad Program Chem Engn, CP 676, BR-13565905 Sao Carlos, SP - Brazil

^[2] Sao Paulo State Univ UNESP, Sch Pharmaceut Sci, Dept Bioproc & Biotechnol, BR-14801902 Araraquara, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Applied Biochemistry and Biotechnology; v. 188, n. 3, p. 706-719, JUL 2019.
• Citações Web of Science: 1

Resumo

Clavulanic acid (CA) is frequently prescribed for treatment of bacterial infections. Despite the large number of studies concerning CA production, there is still a need to search for more effective and productive processes because it is mainly produced by biochemical route and is chemically unstable. This paper evaluates the influence of acid and cold stresses on CA production by Streptomyces clavuligerus in bench scale stirred tank bioreactor. Four batch cultures were conducted at constant pH (6.8 or 6.3) and temperature (30, 25, or 20 degrees C) and five batch cultures were performed with application of acid stress (pH reduction from 6.8 to 6.3), cold stress (reduction from 30 to 20 degrees C), or both. The highest maximum CA concentration (684.4mgL(-1)) was obtained in the culture conducted at constant temperature of 20 degrees C. However, the culture under acid stress, in which the pH was reduced from 6.8 to 6.3 at a rate of 0.1 pH unit every 6h, provided the most promising result, exhibiting a global yield coefficient of CA relative to cell formation (Y-CA/X) of 851.1mg(CA)g(X)(-1). High Y-CA/X values indicate that a small number of cells are able to produce a large amount of antibiotic with formation of smaller amounts of side byproducts. This could be especially attractive for decreasing the complexity and cost of the downstream processing, enhancing CA production. (AU)

• Processo FAPESP: 14/16424-7 - Otimização e aumento de escala do processo de extração líquido-líquido com líquidos iônicos (LIs) como ferramenta de separação sustentável do biofármaco antileucêmico L-asparaginase (ASPase)
• Beneficiário: Jorge Pereira
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores