Fnr Negatively Regulates Prodigiosin Synthesis in Serratia sp. ATCC 39006 During Aerobic Fermentation

Abstract

The well-known Crp/Fnr family regulator Fnr has long been recognized as an oxygen sensor to regulate multiple biological processes, including the switch between aerobic/anaerobic metabolism, nitrogen fixation, bioluminescence, infection, and virulence. In most cases, Fnr was found to be active under anaerobic conditions. However, its role in aerobic antibiotic metabolism has not yet been revealed. In this research, we report that in the model organism, Serratia sp. ATCC 39006, Fnr (Ser39006_013370) negatively regulates prodigiosin production by binding to the spacer between the −10 and −35 region in the promoter of prodigiosin biosynthetic gene cluster under aerobic conditions. Fnr was also shown to modulate the anti-bacterial activity and motility by regulating pathway-specific regulatory genes, indicating that Fnr acts as a global regulator in Serratia sp. ATCC 39006. For the first time, we describe that Fnr regulates antibiotic synthesis in the presence of oxygen, which expands the known physiological functions of Fnr and benefits the further investigation of this important transcriptional regulator.

Transcriptional factor OmpR positively regulates prodigiosin biosynthesis in Serratia marcescens FZSF02 by binding with the promoter of the prodigiosin cluster

“…Prodigiosin was a kind of bacterial secondary metabolites produced mainly by many S. marcescens strains. Various regulating genes involved in prodigiosin biosynthesis have been found in the past two decades, but new regulators, such as RcsB ( Pan et al, 2021 ), CpxA/R ( Qiu et al, 2021 ) and Fnr ( Sun et al, 2021 ), have still been reported continuously. Research of the these genes may help to uncover the regulatory mechanism behind prodigiosin biosynthesis in S. marcescens .…”

Prodigiosin: unveiling the crimson wonder – a comprehensive journey from diverse bioactivity to synthesis and yield enhancement

“…ATCC 39006 under aerobic conditions. There is a Fnr binding site between the −10 and − 35 regions of pigA , which inhibits the synthesis of PG by disrupting the binding of the promoter and RNA polymerase ( Sun et al, 2021 ).…”

“…For the former, Fnr negatively regulates carbapenem biosynthesis through CarR, a gene that can encode a pathway specific activator of bacteriostatic carbapenems; For the latter, Fnr can enhance the expression of flagellar genes, which is conducive to bacterial motility. Therefore, it can be seen that knocking out or modifying a gene has both advantages and disadvantages for the bacteria, and the appropriate method should be selected according to the actual situation ( Sun et al, 2021 ). In one study, researchers introduced clusters of biosynthetic genes encoding PGs into Pseudomonas putida and used genome editing tools to make auxiliary proteins required for polyketide synthases (PKSs) and NRPSs more available, leading to increased PG production ( Cook et al, 2021 ).…”

Biotechnological advances for improving natural pigment production: a state-of-the-art review

“…Typical pigment-producing microorganisms include Phaffia rhodozyma (yeast, producing red pigments—carotenoids), Monascus sp (fungus, producing monascus red pigments), Blakeslea trispora (fungus, producing orange pigments like beta-carotene), Streptomyces cyaneus (fungus, producing black pigment—melanin), and Serratia sp (bacteria, producing red pigment—prodigiosin) (Chao et al 2018 ; El-Batal et al 2017 ; Kim and Ku 2018 ; Mussagy et al 2021 ; Sun et al 2021 ). Traditional random mutagenesis using ultraviolet (UV), 1-methyl-3-nitro-1-nitrosoguanidine (NTG) and ethyl methane sulfonate (EMS) have greatly improved microbial pigment production (Yolmeh and Khomeiri 2016 ; Yolmeh et al 2017 ).…”