Department for Sustainability, Division of Biotechnologies and Agroindustry, Italian National Agency for New Technologies, Energy and Sustainable Economic Development (ENEA), Trisaia Research Centre, SS 106 Jonica, Km 419+500, Rotondella, 75026, Matera, Italy.
Curr Microbiol. 2019 Dec;76(12):1487-1494. doi: 10.1007/s00284-019-01764-y. Epub 2019 Sep 7.
Iturin A is a very important cyclic lipopeptide produced by several B. subtilis strains and has large commercial and therapeutic application potentials but its production on industrial scale has not been realized yet. In the present study, we have observed that the strain ET-1 of Bacillus subtilis, a producer of Iturin A, can present at least three different colony morphologies, which we arbitrarily called Rough, Smooth, and Mucoid morphotypes (R-, S-, and M-form). Performing HPLC analysis, a significant difference between the amounts of Iturin A produced by the three morphotypes was found. The morphotype R-form showed the highest productivity with yields about 10 and 100 times higher than morphotypes S and M, respectively. The results show that the production of Iturin A by B. subtilis could be strongly influenced by the phenotypic heterogeneity of cells within the inoculum. Indeed, we have observed that, pasteurizing the inoculum before seeding in order to improve the homogeneity removing the phenotypes less able to synthesize the Iturin A, its yields in a bench-scale production could be significantly improved. This can represent an important control factor also at industrial scale to improve the Iturin A yields, the robustness, the replicability, and consequently the cost-effectiveness of fermentation processes.
依枯草菌素 A 是一种非常重要的环状脂肽，由几种枯草芽孢杆菌菌株产生，具有很大的商业和治疗应用潜力，但尚未在工业规模上实现生产。在本研究中，我们观察到枯草芽孢杆菌 ET-1 菌株，一种依枯草菌素 A 的生产者，至少可以呈现出三种不同的菌落形态，我们任意将其称为粗糙型、光滑型和黏液型（R-、S-和 M-形态）。通过 HPLC 分析，发现这三种形态产生的依枯草菌素 A 的数量存在显著差异。R 形态表现出最高的生产力，其产量分别比 S 和 M 形态高出约 10 和 100 倍。结果表明，枯草芽孢杆菌产生依枯草菌素 A 的能力可能受到接种物中细胞表型异质性的强烈影响。事实上，我们已经观察到，在接种前对接种物进行巴氏消毒以提高均匀性，去除不太能够合成依枯草菌素 A 的表型，可以显著提高其在中试生产中的产量。这可以在工业规模上代表一个重要的控制因素，以提高依枯草菌素 A 的产量、稳健性、可重复性，从而提高发酵过程的成本效益。
