AUTHOR=Dinius Anna , Schrinner Kathrin , Schrader Marcel , Kozanecka Zuzanna Justyna , Brauns Henry , Klose Leon , Weiß Hannah , Kwade Arno , Krull Rainer 

TITLE=Morphology engineering for novel antibiotics: Effect of glass microparticles and soy lecithin on rebeccamycin production and cellular morphology of filamentous actinomycete Lentzea aerocolonigenes

JOURNAL=Frontiers in Bioengineering and Biotechnology

VOLUME=Volume 11 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2023.1171055

DOI=10.3389/fbioe.2023.1171055

ISSN=2296-4185

ABSTRACT=Lentzea aerocolonigenes as an actinomycete is a natural producer of the antibiotic and antitumoral drug rebeccamycin. Due to the filamentous cellular morphology handling in cultivations is challenging which is why morphology engineering techniques are mandatory to enhance productivity. One promising approach described in literature is the addition of mineral particles in the micrometer range to precisely adjust cellular morphology and the corresponding product synthesis (microparticle-enhanced cultivation, MPEC). Within this study glass microparticles are introduced as a novel supplementation type for bioprocess intensification in filamentous organisms. Several investigations were conducted to screen for an optimal particle set-up including particle size and concentration in regard to their impact and effects on enhanced productivity, microparticle incorporation behavior into the biopellets, viability of pellets and morphological changes. Glass microparticles (10 g L-1) with a median diameter of 7.9 µm, for instance, induced an up to 4-fold increase in product synthesis accompanied by overall enhanced viability of biomass. Furthermore, structural elucidations showed biopellets isolated from MPEC tend to be of lower hyphal density than unsupplemented control pellets. In this context, oxygen microprofiling was conducted to better understand how internal structural changes interwind with oxygen supply into the pellets. Here, the resulting oxygen profiles are of a contradictive trend of steeper oxygen consumption with increasing glass microparticle supplementation. Eventually, MPEC was combined with another promising cultivation strategy, the supplementation of soy lecithin (7.5 g L-1), to further increase the cultivation performance. Combining both techniques in an optimized set-up resulted in a rebeccamycin concentration of 213 mg L-1 after 10 d of cultivation, the highest value published so far for microparticle-supplemented shake flask cultivations of L. aerocolonigenes.