Actinomycetes scale‐up for the production of the antibacterial, nocathiacin

Abstract

An Amycolatopsis fastidiosa culture, which produces the nocathiacin class of antibacterial compounds, was scaled up to the 15,000 L working volume. Lower volume pilot fermentations (600, 900, and 1,500 L scale) were conducted to determine process feasibility at the 15,000 L scale. The effects of inoculum volume, impeller tip speed, volumetric gas flow rate, superficial gas velocity, backpressure, and sterilization heat stress were examined to determine optimal scale-up operating conditions. Inoculum volume (6 vs. 2 vol %) and medium sterilization (R(o) of 68 vs. 92 min(-1)) had no effect on productivity or titer, and higher impeller tip speeds (2.1 vs. 2.9 m/s) had a slight effect (20% decrease). In contrast, higher backpressure, incorporating increased head pressure at the 15,000 L scale (1.2 vs. 0.7 kg/cm(2)) and low gas flow rates (0.25 vs. 0.8 vvm), appeared to be problematic (40-50% decrease). High off-gas CO2 levels were likely reasons for observed lower productivity. Consequently, air flow rate for this 25-fold scale-up (600-15,000 L) was controlled to match off-gas CO2 profiles of acceptable smaller scale batches to maintain levels below 0.5%. The 15,000 L-scale fermentation achieved an expected nocathiacin I titer of 310 mg/L after 7 days. Other on-line data (i.e., pH, oxygen uptake rate, and CO2 evolution rate) and off-line data (i.e., analog production, glucose utilization, ammonium production, and dry cell weight) at the 15,000 L scale also tracked similarly to the smaller scale, demonstrating successful fermentation scale-up.

A new marine microorganism strain L0804: taxonomy and characterization of active compounds from its metabolite

“…Among microorganisms, actinomycetes are one of the most investigated groups particularly members of the genus Streptomyces from which, a large number of antibiotics were obtained and reported (Alan and James 2007;Lyudmila et al 2008;Junker et al 2009;Koch and Loffler 2009). Those promising results have emphasized the need to continue the research in this way.…”

Biologically active secondary metabolites from Actinomycetes

“…Amycolatopsis fastidiosa produces nocathiacins and thiazomycins, which exhibit antibacterial activity [43]. Thiazomycin and thiazomycin A (2) are thiazolyl peptides (thiopeptides) that are potent against Gram-positive bacteria (MIC=0.002~0.064 µg/ml for thiazomycin, 0.002~0.25 µg/ml for thiazomycin A) ( Figure 2) [42,44].…”

VOLUMETRIC POWER INPUT AS A RELIABLE PARAMETER FOR SCALE-UP FROM SHAKE FLASK TO STIRRED-TANK BIOREACTOR: PRODUCTION OF A RECOMBINANT GLYCOPROTEIN BY Streptomyces lividans

“…In addition, for commercial production, many bioprocesses need to occur on a larger scale than in shake flasks; therefore, it is necessary to scale-up these to bioreactors, in which, it is possible to monitor and control several variables of the process independently (Tajsoleiman et al 2019). Various criteria have been proposed for scaling-up biotechnological processes, such as the volumetric mass transfer coefficient (k L a) (Humphrey, 1998;Garcia-Ochoa and Gomez, 2009;, the oxygen transfer rate (Garcia-Ochoa and Gomez, 2009;Raval et al 2017), impeller tip speed (Junker et al 2009), mixing/circulation time (Junker, 2004), and volumetric power input (P/V) (Pérez et al 2006;Rocha-Valadez et al 2006Xu et al 2017). P/V is a global parameter defined as the amount of energy required to maintain the fluid motion within a vessel for a given period of time (Marques et al 2010), and it is associated with the physical phenomena that occur in the bioreactor, such as oxygen transfer, removal of carbon dioxide, macro and micro mixing, turbulence intensity, uniformity of the liquid phase, and hydrodynamic stress (Lara 2011, Olmos et al 2013.…”