Characterization of an Lrp/AsnC family regulator SCO3361, controlling actinorhodin production and morphological development in Streptomyces coelicolor

Abstract

Lrp/AsnC family regulators have been found in many bacteria as crucial regulators controlling diverse cellular processes. By genomic alignment, we found that SCO3361, an Lrp/AsnC family protein from Streptomyces coelicolor, shared the highest similarity to the SACE_Lrp from Saccharopolyspora erythraea. Deletion of SCO3361 led to dramatic reduction in actinorhodin (Act) production and delay in aerial mycelium formation and sporulation on solid media. Dissection of the mechanism underlying the function of SCO3361 in Act production revealed that it altered the transcription of the cluster-situated regulator gene actII-ORF4 by directly binding to its promoter. SCO3361 was an auto-regulator and simultaneously activated the transcription of its adjacent divergently transcribed gene SCO3362. SCO3361 affected aerial hyphae formation and sporulation of S. coelicolor by activating the expression of amfC, whiB, and ssgB. Phenylalanine and cysteine were identified as the effector molecules of SCO3361, with phenylalanine reducing the binding affinity, whereas cysteine increasing it. Moreover, interactional regulation between SCO3361 and SACE_Lrp was discovered for binding to each other's target gene promoter in this work. Our findings indicate that SCO3361 functions as a pleiotropic regulator controlling secondary metabolism and morphological development in S. coelicolor.

Structural and functional comparison of Saccharomonospora azurea strains in terms of primycin producing ability

“…Genes corresponding to Lrp/AsnC family transcriptional regulators were found substantially up-regulated in high-primycin producer strains. Present findings were in agreement with previously reported facts that, genes encoding the Lrp/AsnC family transcriptional regulators (SCO2140 and SCO3361) act as positive regulators of antibiotic production in S. coelicolor (Liu et al 2017 ; Yu et al 2016 ).…”

Enhancement of precursor amino acid supplies for improving bacitracin production by activation of branched chain amino acid transporter BrnQ and deletion of its regulator gene lrp in Bacillus licheniformis

“…The Lrp family regulators have been confirmed as the important transcriptional factors involved in physiological metabolism, including DNA repair and recombination, antibiotic synthesis, morphological development, amino acid distribution, etc., and the regulation network of Lrp have been analyzed in C. glutamicum , S. erythraea , E. coli and Archaea [ 10 , 11 , 15 , 27 , 28 ]. In C. glutamicum , the regulation of Lrp on amino acid distribution was attributed to the expression of BrnFE, an amino acid transporter responsible for BCAA and l -methionine exports [ 12 , 13 ].…”

“…Moreover, Liu et al implied that deletion of Lrp family regulator gene SACE-Lrp improved the accumulations of BCAAs, which led to a 25% increase of erythromycin yield in Saccharopolyspora erythraea [ 14 ]. Additionally, the Lrp analogous regulator SCO3361 was proven to be a direct regulator for actinorhodin synthetase in S. coelicolor [ 15 ]. Based on these previous results, the regulator Lrp might also play an important role in BCAA distributions and antibiotic synthesis in B. licheniformis .…”

Recent advances in natural products exploitation in Streptomyces via synthetic biology

“…According to the presence of unique regulatory mechanisms that govern the expression of individual natural products, a widely applicable synthetic biology approach based on the promoter profiling has been developed . Either introduction of strong promoters upstream of main biosynthetic operon and pathway‐specific active regulators, or deletion of negative regulators has been reported to improve the natural products production significantly . A useful platform named plug‐and‐play has been developed and used in many cryptic gene clusters activations and BGCs overexpression .…”