Oxidative stress induces alkaloid production in <i>Uncaria tomentosa</i> root and cell cultures in bioreactors

<jats:title>Abstract</jats:title><jats:p>The effect of oxidative stress on indole alkaloids accumulation by cell suspensions and root cultures of <jats:italic>Uncaria tomentosa</jats:italic> in bioreactors was investigated. Hydrogen peroxide (H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub>, 200 μM) added to <jats:italic>U</jats:italic>. <jats:italic>tomentosa</jats:italic> cell suspension cultures in shaken flasks induced the production of monoterpenoid oxindole alkaloids (MOA) up to 40.0 μg/L. In a stirred tank bioreactor, MOA were enhanced by exogenous H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub> (200 μM) from no detection up to 59.3 μg/L. Root cultures grew linearly in shaken flasks with a μ=0.045 days<jats:sup>−1</jats:sup> and maximum biomass of 12.08±1.24 g DW/L (at day 30). Roots accumulated 3α‐dihydrocadambine (DHC) 2354.3±244.8 μg/g DW (at day 40) and MOA 348.2±32.1 μg/g DW (at day 18). Exogenous addition of H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub> had a differential effect on DHC and MOA production in shaken flasks. At 200 μM H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub>, MOA were enhanced by 56% and DHC by 30%; while addition of 800 and 1000 μM H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub>, reduced by 30–40% DHC accumulation without change in MOA. Root cultures in the airlift reactor produced extracellular H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub> with a characteristic biphasic profile after changing aeration. Maximum MOA was 9.06 mg/L at day 60 while at this time roots reached ca. 1 mg/L of DHC. Intracellular H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub> in root cultures growing in the bioreactor was 0.87 μmol/g DW compared to 0.26 μmol/g DW of shaken flasks cultures. These results were in agreement with a higher activity of the antioxidant enzymes superoxide dismutase and peroxidase by 6‐ and 2‐times, respectively. <jats:italic>U</jats:italic>. <jats:italic>tomentosa</jats:italic> roots growing in the airlift bioreactor were exposed to an oxidative stress and their antioxidant system was active allowing them to produce oxindole alkaloids.</jats:p>