Brazilian Journal of Microbiology Brazilian Journal of Microbiology
Braz J Microbiol 2018;49:832-9 - Vol. 49 Num.4 DOI: 10.1016/j.bjm.2018.01.006
Biotechnology and Industrial Microbiology
Screening of medium constituents for clavulanic acid production by Streptomyces clavuligerus
Kaio César da Silva Rodriguesa, Arianne Tairyne de Souzab, Alberto Colli Badinoa, Danielle Biscaro Pedrollic, Marcel Otavio Cerric,,
a Universidade Federal de São Carlos, Departamento de Engenharia Química, São Carlos, SP, Brazil
b Universidade Federal de São João del-Rei, Campus Alto Paraopeba, Departamento de Química, Biotecnologia e Bioprocessos, Ouro Branco, MG, Brazil
c Universidade Estadual Paulista (UNESP), Departamento de Bioprocessos e Biotecnologia, Araraquara, SP, Brazil
Received 15 August 2017, Accepted 24 January 2018
Abstract

Clavulanic acid is a β-lactam compound with potent inhibitory activity against β-lactamases. Studies have shown that certain amino acids play essential roles in CA biosynthesis. However, quantitative evaluations of the effects of these amino acids are still needed in order to improve CA production. Here, we report a study of the nutritional requirements of Streptomyces clavuligerus for CA production. Firstly, the influence of the primary nitrogen source and the salts composition was investigated. Subsequently, soybean protein isolate was supplemented with arginine (0.0–3.20gL−1), threonine (0.0–1.44gL−1), ornithine (0.0–4.08gL−1), and glutamate (0.0–8.16gL−1), according to a two-level central composite rotatable design. A medium containing ferrous sulfate yielded CA production of 437mgL−1, while a formulation without this salt produced only 41mgL−1 of CA. This substantial difference suggested that Fe2+ is important for CA biosynthesis. The experimental design showed that glutamate and ornithine negatively influenced CA production while arginine and threonine had no influence. The soybean protein isolate provided sufficient C5 precursor for CA biosynthesis, so that supplementation was unnecessary. Screening of medium components, together with experimental design tools, could be a valuable way of enhancing CA titers and reducing the process costs.

Keywords
Clavulanic acid, Streptomyces clavuligerus, Ferrous sulfate, Amino acids supplementation
Braz J Microbiol 2018;49:832-9 - Vol. 49 Num.4 DOI: 10.1016/j.bjm.2018.01.006