Comparative transcriptome analysis reveals metabolic regulation of prodigiosin in Serratia marcescens

Abstract

Prodigiosin is a secondary metabolite mainly produced at 30 °C in Serratia marcescens, but it can hardly be synthetized at 37 °C or higher. In this study, we provide insight into the metabolic regulation of prodigiosin synthesis in response to temperature through transcriptome sequencing. The analysis of the function of differentially expressed genes suggested that temperature resulted in significant alteration of the metabolic pathways between 30 and 37 °C. Specifically, 30 °C favored transcriptional expression of the pig gene cluster. At the same time, the carbon flux was redistributed to pathways of pyruvate, proline, serine, especially homoserine, cystathionine, homocysteine, methionine, and s-adenosylmethionine metabolism, all involved in prodigiosin biosynthesis, and was finally increased towards the prodigiosin synthesis pathway in S. marcescens at 30 °C. Interestingly, results further confirmed increased transcriptional level of five regulators (LuxS, RpoS, Hfq, EepR, CRP), and decreased content of hexS through qPCR. Finally, successful co-overexpression of mmuM and metK, related to homocysteine, methionine, and s-adenosylmethionine metabolism, in the chromosome of JNB5-1 (JNB5-1/MK) resulted in increased prodigiosin titer up to 7.57 g/L in JNB5-1/MK at 30 °C, which was 41.2% higher than that in JNB5-1. Our transcriptome analysis provides further insight into the strain's response to temperature changes at the transcription level, which is of great significance for improving the production of prodigiosin.