Fine-tuning gene expression of regulator AdmX for improved biosynthesis of andrimid in Erwinia persicina BST187

Appl Microbiol Biotechnol. 2023 Nov;107(22):6775-6788. doi: 10.1007/s00253-023-12770-3. Epub 2023 Sep 16.

Abstract

Andrimid is a potent antibiotic that inhibits acetyl-CoA carboxylase. However, its low biological yield and complex chemical synthesis have hindered its large-scale application. In this study, we found that the LysR-type transcriptional activator AdmX controls andrimid yield by adjusting its expression level in the andrimid-producing bacterium Erwinia persicina strain BST187. Our results showed that gradually increasing of admX transcriptional levels significantly improved andrimid yield, while the yield declined when admX was overexpressed excessively. To further estimate the effect of AdmX on andrimid promotion, we fitted and developed a model which was y = -0.5576x2 + 61.945x + 800.63 (R2 = 0.9591), where x represents the admX transcriptional level and y represents andrimid yield. Andrimid yield of admX overexpression strain BST187ΔadmX/pET28a-Pgap-1::admX was greatly improved by 260%, which was reported for the first time that andrimid yield could be promoted by genetic engineering. Thus, this study provides important insights that the biosynthesis of andrimid would be improved by bioengineering and sheds lights on the potential application of andrimid in both biomedicine and bioagricultural manipulation with its large-scale production in the future. KEY POINTS: • Andrimid production can be greatly promoted by genetic engineering on non-model chassis. • The relationship between AdmX abundance and andrimid yield in Erwinia persicina strain BST187 might be parabolic. • Erwinia persicina BST187 combined with chassis modification enable the promising applications in andrimid industrialization.

Keywords: AdmX; Andrimid; Bioengineering; Transcription regulation; Yield improvement.