Biosynthesis of Polyketides in Streptomyces

Risdian, Chandra; Mozef, Tjandrawati; Wink, Joachim

doi:10.3390/microorganisms7050124

Cited by 93 publications

(71 citation statements)

References 101 publications

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“…Monensin biosynthetic gene cluster (mon) has been sequenced, and the functions have been partially characterized [18,19]. Eight separate type I polyketide synthases (PKSs) (MonAI to MonAVIII) were proposed to be responsible for assembling short chain acyl-CoA precursors into carbon backbone of monensin molecule [20]. The tailoring enzymes MonBI, MonBII and MonCI are involved in the oxidative cyclization of a linear polyketide intermediate [21][22][23]; MonD hydroxylases at C-26, and MonE methylates hydroxyl group at C-3 [24].…”

Section: Introductionmentioning

confidence: 99%

Regulatory Patterns of Crp on Monensin Biosynthesis in Streptomyces cinnamonensis

Lin

Zhang

et al. 2020

Microorganisms

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Monensin, produced by Streptomyces cinnamonensis, is a polyether ionophore antibiotic widely used as a coccidiostat and a growth-promoting agent in agricultural industry. In this study, cyclic AMP receptor protein (Crp), the global transcription factor for regulation of monensin biosynthesis, was deciphered. The overexpression and antisense RNA silencing of crp revealed that Crp plays a positive role in monensin biosynthesis. RNA sequencing analysis indicated that Crp exhibited extensive regulatory effects on genes involved in both primary metabolic pathways and the monensin biosynthetic gene cluster (mon). The primary metabolic genes, including acs, pckA, accB, acdH, atoB, mutB, epi and ccr, which are pivotal in the biosynthesis of monensin precursors malonyl-CoA, methylmalonyl-CoA and ethylmalonyl-CoA, are transcriptionally upregulated by Crp. Furthermore, Crp upregulates the expression of most mon genes, including all PKS genes (monAI to monAVIII), tailoring genes (monBI-monBII-monCI, monD and monAX) and a pathway-specific regulatory gene (monRI). Enhanced precursor supply and the upregulated expression of mon cluser by Crp would allow the higher production of monensin in S. cinnamonensis. This study gives a more comprehensive understanding of the global regulator Crp and extends the knowledge of Crp regulatory mechanism in Streptomyces.

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Section: Introductionmentioning

confidence: 99%

Regulatory Patterns of Crp on Monensin Biosynthesis in Streptomyces cinnamonensis

Lin

Zhang

et al. 2020

Microorganisms

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“…Streptomyces generally synthesize their antibiotics using large enzymatic complexes like polyketide synthases (PKSs), nonribosomal peptide synthases (NRPSs) or a combination of both. These large multienzyme complexes use many different domains to accomplish chemical modifications that can produce a wide range of antibiotics [20,21].…”

Section: Antibiotic Synthesismentioning

confidence: 99%

“…Construction of the antibiotic proceeds through a series of enzyme-mediated steps typically involving acyltransferases, ketidesynthases and other enzymes leading to the formation of the backbone of the polyketide antibiotic. The growing antibiotic can be subject to further modifications that might include cyclization, decarboxylation, dehydration, reduction and methylation [21] (Fig. 1).…”

Section: Antibiotic Synthesismentioning

confidence: 99%

Streptomyces from traditional medicine: sources of new innovations in antibiotic discovery

Quinn

Banat

Abdelhameed

et al. 2020

Journal of Medical Microbiology

150

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Given the increased reporting of multi-resistant bacteria and the shortage of newly approved medicines, researchers have been looking towards extreme and unusual environments as a new source of antibiotics. Streptomyces currently provides many of the world’s clinical antibiotics, so it comes as no surprise that these bacteria have recently been isolated from traditional medicine. Given the wide array of traditional medicines, it is hoped that these discoveries can provide the much sought after core structure diversity that will be required of a new generation of antibiotics. This review discusses the contribution of Streptomyces to antibiotics and the potential of newly discovered species in traditional medicine. We also explore how knowledge of traditional medicines can aid current initiatives in sourcing new and chemically diverse antibiotics.

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“…polyketides, pigments, flavonoids) have been characterized (Gomes et al ; Rani et al ). Among the secondary metabolites found in Streptomyces , polyketides are one of the most abundant classes of compounds with remarkable structural diversity and biological activities (reviewed by Risdian et al, ). They are biosynthesized by repetitive Claisen condensations of extender units derived from malonyl‐coenzyme A with an activated carboxylic acid starter unit in a reaction sequence divergently related to fatty acid biosynthesis.…”

Section: Introductionmentioning

confidence: 99%

Unique secondary metabolites of a Streptomyces strain isolated from extreme salty wetland show antioxidant and antibacterial activities

Riahi

Hosni²,

Raïes

et al. 2019

J Appl Microbiol

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Aims To identify and assess the biological activities of the crude extract of a Streptomyces isolate from a salty wetland, an extreme environment likely to induce secondary metabolism of micro‐organisms. Methods and Results The crude extract from the isolate Streptomyces lanatus strain AR2 displayed antibacterial activity against Gram‐positive bacteria (MICs ranging from 5 to 50 μg ml−1) and antioxidant activity as revealed in DPPH (2,2‐diphenyl‐1‐picrylhydrazyl) assay (IC50 of 0·74 mg ml−1), ferric reducing antioxidant power (IC50 of 1·12 mg ml−1) and metal‐chelating power (IC50 of 1·84 mg ml−1) assays. Accordingly, the extract attenuated the H2O2‐induced oxidative stress in the eukaryotic cell model Saccharomyces cerevisiae, assessed by flow cytometry. The profiling of secondary metabolites by HPLC‐PDA‐ESI‐MS/MS revealed the presence of 17 compounds, some of which reported in Streptomyces for the first time to the best of our knowledge: genistein‐7‐O‐glucuronide, naringenin‐7‐O‐rutinoside and resveratrol. Conclusions Streptomyces lanatus AR2 produced unique polyketides and phenolic compounds with noticeable bioactivities, allowing adaptation to the extreme environment. Significance and Impact of the Study Sabkhat Seijoumi salty wetland represents a potential niche for Streptomyces yielding useful natural products for biotechnological, pharmaceutical and medical applications.

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Biosynthesis of Polyketides in Streptomyces

Cited by 93 publications

References 101 publications

Regulatory Patterns of Crp on Monensin Biosynthesis in Streptomyces cinnamonensis

Regulatory Patterns of Crp on Monensin Biosynthesis in Streptomyces cinnamonensis

Streptomyces from traditional medicine: sources of new innovations in antibiotic discovery

Unique secondary metabolites of a Streptomyces strain isolated from extreme salty wetland show antioxidant and antibacterial activities

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