AdpA Positively Regulates Morphological Differentiation and Chloramphenicol Biosynthesis in Streptomyces venezuelae

Płachetka, Małgorzata; Krawiec, Michał; Zakrzewska‐Czerwińska, Jolanta; Wolański, Marcin

doi:10.1128/spectrum.01981-21

Cited by 6 publications

(4 citation statements)

References 85 publications

(117 reference statements)

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“…albulus . It’s recently reported that the posttranslational regulation is a possible new mechanism that may regulate AdpA protein abundance in Streptomyces cells [ 83 ]. Consequently, we surmise that regulation at the translational level by the UUA codon and posttranslational regulation might cause different AdpA protein abundances in the mutants studied in this paper.…”

Section: Discussionmentioning

confidence: 99%

AdpA, a developmental regulator, promotes ε-poly-l-lysine biosynthesis in Streptomyces albulus

et al. 2022

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Background AdpA is a global regulator of morphological differentiation and secondary metabolism in Streptomyces, but the regulatory roles of the Streptomyces AdpA family on the biosynthesis of the natural product ε-poly-l-lysine (ε-PL) remain unidentified, and few studies have focused on increasing the production of ε-PL by manipulating transcription factors in Streptomyces. Results In this study, we revealed the regulatory roles of different AdpA homologs in ε-PL biosynthesis and morphological differentiation and effectively promoted ε-PL production and sporulation in Streptomycesalbulus NK660 by heterologously expressing adpA from S.neyagawaensis NRRLB-3092 (adpASn). First, we identified a novel AdpA homolog named AdpASa in S.albulus NK660 and characterized its function as an activator of ε-PL biosynthesis and morphological differentiation. Subsequently, four heterologous AdpA homologs were selected to investigate their phylogenetic relationships and regulatory roles in S.albulus, and AdpASn was demonstrated to have the strongest ability to promote both ε-PL production and sporulation among these five AdpA proteins. The ε-PL yield of S.albulus heterologously expressing adpASn was approximately 3.6-fold higher than that of the control strain. Finally, we clarified the mechanism of AdpASn in enhancing ε-PL biosynthesis and its effect on ε-PL polymerization degree using real-time quantitative PCR, microscale thermophoresis and MALDI-TOF–MS. AdpASn was purified, and its seven direct targets, zwf, tal, pyk2, pta, ack, pepc and a transketolase gene (DC74_2409), were identified, suggesting that AdpASn may cause the redistribution of metabolic flux in central metabolism pathways, which subsequently provides more carbon skeletons and ATP for ε-PL biosynthesis in S.albulus. Conclusions Here, we characterized the positive regulatory roles of Streptomyces AdpA homologs in ε-PL biosynthesis and their effects on morphological differentiation and reported for the first time that AdpASn promotes ε-PL biosynthesis by affecting the transcription of its target genes in central metabolism pathways. These findings supply valuable insights into the regulatory roles of the Streptomyces AdpA family on ε-PL biosynthesis and morphological differentiation and suggest that AdpASn may be an effective global regulator for enhanced production of ε-PL and other valuable secondary metabolites in Streptomyces.

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Section: Discussionmentioning

confidence: 99%

AdpA, a developmental regulator, promotes ε-poly-l-lysine biosynthesis in Streptomyces albulus

et al. 2022

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“…Whatever the real mechanism is, it is useful practically because an improved dispersed growth of strains is one of the key requirements for industrial utilization. Curiously, the very recent data provided by Płachetka et al [64] have shown that the AdpA ortholog in Streptomyces venezuelae does not interact with its oriC region. Likely, this is one of the main factors explaining the dispersed growth common for S. venezuelae.…”

Section: Discussionmentioning

confidence: 99%

Genetic Engineering of Streptomyces ghanaensis ATCC14672 for Improved Production of Moenomycins

2021

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Streptomycetes are soil-dwelling multicellular microorganisms famous for their unprecedented ability to synthesize numerous bioactive natural products (NPs). In addition to their rich arsenal of secondary metabolites, Streptomyces are characterized by complex morphological differentiation. Mostly, industrial production of NPs is done by submerged fermentation, where streptomycetes grow as a vegetative mycelium forming pellets. Often, suboptimal growth peculiarities are the major bottleneck for industrial exploitation. In this work, we employed genetic engineering approaches to improve the production of moenomycins (Mm) in Streptomyces ghanaensis, the only known natural direct inhibitors of bacterial peptidoglycan glycosyltransferses. We showed that in vivo elimination of binding sites for the pleiotropic regulator AdpA in the oriC region strongly influences growth and positively correlates with Mm accumulation. Additionally, a marker- and “scar”-less deletion of moeH5, encoding an amidotransferase from the Mm gene cluster, significantly narrows down the Mm production spectrum. Strikingly, antibiotic titers were strongly enhanced by the elimination of the pleiotropic regulatory gene wblA, involved in the late steps of morphogenesis. Altogether, we generated Mm overproducers with optimized growth parameters, which are useful for further genome engineering and chemoenzymatic generation of novel Mm derivatives. Analogously, such a scheme can be applied to other Streptomyces spp.

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“…More than 70% of commercially important antibiotics are produced by this group of bacteria [2]. Some of the known antibiotics related to Streptomyces are streptomycin [3], tetracycline [4], chloramphenicol [5], kanamycin [6], fosfomycin [7], daptomycin [8], and platensimycin [9]. Besides the antibiotic group, Streptomyces can also produce antioxidant compounds such as thiazostatin A and B [10], protocatechualdehyde [11], and 2-(N-acetylcysteinyl)amido-2-deoxy-α-D-glucopyranosyl-myoinositol (U17) [12].…”

Section: Introductionmentioning

confidence: 99%

Production of antibacterial and antioxidant agents by Actinobacteria using soybean meal as a nitrogen source

Risdian,

Endah,

Saraswaty

et al. 2023

IOP Conf. Ser.: Earth Environ. Sci.

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Actinobacteria are mainly found in soil and some of them have properties that are common to bacteria and fungi, despite having quite distinct characteristics. Unlike bacterial colonies in general, which are clearly slimy and grow rapidly, some groups of actinobacteria colonies grow slowly by showing a powdery consistency and are tightly attached to the agar surface. Observations on a colony under the microscope showed that many of them form asexual spores for their reproduction. Many metabolite compounds generated by actinobacteria have promising activities like antioxidant and antagonistic activity against bacteria and fungi. The production of these compounds depends not only on the strain of the organism but also on the medium in which it is grown and the growth conditions. Moreover, agricultural by-products such as soybean meal are known to have high protein content, thus it can be potentially used as an alternative media for actinobacteria. In this research, ten actinobacterial strains were isolated from the soil. After seven days of cultivation with the medium containing soybean meal, the cultures were subjected to ethyl acetate extraction. Five extracts exhibited antibacterial properties against Bacillus subtilis with a zone of inhibition ranging from 10–14 mm. One extract could strongly inhibit Staphylococcus aureus with an inhibition zone of 21 mm. However, none of them were active against Escherichia coli. Five extracts demonstrated antioxidant DPPH radical scavenging activity with more than 40%.

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AdpA Positively Regulates Morphological Differentiation and Chloramphenicol Biosynthesis in Streptomyces venezuelae

Cited by 6 publications

References 85 publications

AdpA, a developmental regulator, promotes ε-poly-l-lysine biosynthesis in Streptomyces albulus

AdpA, a developmental regulator, promotes ε-poly-l-lysine biosynthesis in Streptomyces albulus

Genetic Engineering of Streptomyces ghanaensis ATCC14672 for Improved Production of Moenomycins

Production of antibacterial and antioxidant agents by Actinobacteria using soybean meal as a nitrogen source

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