Heterologous Expression and Manipulation of Three Tetracycline Biosynthetic Pathways

Wang, Peng; Kim, Won-Cheol; Pickens, Lauren B.; Gao, Xue; Tang, Yi

doi:10.1002/anie.201205426

Cited by 47 publications

(41 citation statements)

References 34 publications

(48 reference statements)

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“…This enzyme can also perform the equivalent reaction for tetracycline. Closely related enzymes are involved in the same step during biosynthesis of chlorotetracycline (CtcR) and dactylocyclinone (DaCO4) in Streptomyces aureofaciens and Streptomyces rimosus (29,386). Encoded by the oxytetracycline (oxy), chlorotetracycline (ctc), and dactylocyclinone (dac) gene clusters (29), these enzymes are members of the flavin/deazaflavin oxidoreductase (FDOR) superfamily (30) and utilize F 420 H 2 reduced through the action of Fno (387).…”

Section: Streptomycetesmentioning

confidence: 99%

Physiology, Biochemistry, and Applications of F₄₂₀- and F_o-Dependent Redox Reactions

Greening

Ahmed

Mohamed

et al. 2016

Microbiol Mol Biol Rev

152

208

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SUMMARY5-Deazaflavin cofactors enhance the metabolic flexibility of microorganisms by catalyzing a wide range of challenging enzymatic redox reactions. While structurally similar to riboflavin, 5-deazaflavins have distinctive and biologically useful electrochemical and photochemical properties as a result of the substitution of N-5 of the isoalloxazine ring for a carbon. 8-Hydroxy-5-deazaflavin (Fo) appears to be used for a single function: as a light-harvesting chromophore for DNA photolyases across the three domains of life. In contrast, its oligoglutamyl derivative F420is a taxonomically restricted but functionally versatile cofactor that facilitates many low-potential two-electron redox reactions. It serves as an essential catabolic cofactor in methanogenic, sulfate-reducing, and likely methanotrophic archaea. It also transforms a wide range of exogenous substrates and endogenous metabolites in aerobic actinobacteria, for example mycobacteria and streptomycetes. In this review, we discuss the physiological roles of F420in microorganisms and the biochemistry of the various oxidoreductases that mediate these roles. Particular focus is placed on the central roles of F420in methanogenic archaea in processes such as substrate oxidation, C1pathways, respiration, and oxygen detoxification. We also describe how two F420-dependent oxidoreductase superfamilies mediate many environmentally and medically important reactions in bacteria, including biosynthesis of tetracycline and pyrrolobenzodiazepine antibiotics by streptomycetes, activation of the prodrugs pretomanid and delamanid byMycobacterium tuberculosis, and degradation of environmental contaminants such as picrate, aflatoxin, and malachite green. The biosynthesis pathways of Foand F420are also detailed. We conclude by considering opportunities to exploit deazaflavin-dependent processes in tuberculosis treatment, methane mitigation, bioremediation, and industrial biocatalysis.

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Section: Streptomycetesmentioning

confidence: 99%

Physiology, Biochemistry, and Applications of F₄₂₀- and F_o-Dependent Redox Reactions

Greening

Ahmed

Mohamed

et al. 2016

Microbiol Mol Biol Rev

152

208

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“…However, during th e last decade, the most signifi cant insight into OTC biosynthesis has been gained by Tang´s research group at the University of California, Los Angeles (USA) (57)(58)(59)(60)(61)(62)(63).…”

Section: Biosynthetic Pathway Of Tetracycline Antibioticsmentioning

confidence: 99%

“…Based on amino acid sequence analyses, OtcR and Ctc11 (CtcB) from S. aureofaciens share 46 % identity; furthermore, the predicted SARP-binding sites were also identifi ed in the ctc cluster. Interestingly, Wang et al (62) found that the SARP regulator, encoded by ctc11 (ctcB) from the CTC gene cluster (ctc) of S. aureofaciens (36), could activate the transcription of the oxy cluster in the heterologous host Streptomyces coelicolor (62). Since OTC and CTC are structurally highly similar antibiotics, it is reasonable to expect similar biosynthetic and regulatory mechanisms.…”

Section: Regulation Of Tetracycline Biosynthesis and Genes Involved Imentioning

confidence: 99%

“…However, biosynthetic engineering eff orts in TCs are not exhausted, and can be productively applied at the initial steps of TC biosynthesis (e.g. starter unit selection) as well as at the late stages of TC biosynthesis, the so-called post--PKS processing, steps that are oft en of crucial importance for the biological activity of these compounds (26,62). A number of TC structures with a broad range of biological activities have been isolated (Fig.…”

Section: Future Directions In Biosynthetic Engineering Of Tetracyclinmentioning

confidence: 99%

“…A number of TC structures with a broad range of biological activities have been isolated (Fig. 3) and the corresponding gene clusters have been cloned, as recently exemplifi ed by Wang et al (62) and Lukežič et al (25).…”

Section: Future Directions In Biosynthetic Engineering Of Tetracyclinmentioning

confidence: 99%

See 2 more Smart Citations

Biosynthesis of Oxytetracycline by Streptomyces rimosus: Past, Present and Future Directions in the Development of Tetracycline Antibiotics

Petković

Lukežič²,

Šušković

2017

Food Technol. Biotechnol.

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SummaryNatural tetracycline (TC) antibiotics were the fi rst major class of therapeutics to earn the distinction of 'broad-spectrum antibiotics' and they have been used since the 1940s against a wide range of both Gram-positive and Gram-negative pathogens, mycoplasmas, intracellular chlamydiae, rickett siae and protozoan parasites. The second generation of semisynthetic tetracyclines, such as minocycline and doxycycline, with improved antimicrobial potency, were introduced during the 1960s. Despite emerging resistance to TCs erupting during the 1980s, it was not until 2006, more than four decades later, that a third--generation TC, named tigecycline, was launched. In addition, two TC analogues, omadacycline and eravacycline, developed via (semi)synthetic and fully synthetic routes, respectively, are at present under clinical evaluation. Interestingly, despite very productive early work on the isolation of a Streptomyces aureofaciens mutant strain that produced 6-demethyl-7-chlortetracycline, the key intermediate in the production of second-and third-generation TCs, biosynthetic approaches in TC development have not been productive for more than 50 years. Relatively slow and tedious molecular biology approaches for the genetic manipulation of TC-producing actinobacteria, as well as an insuffi cient understanding of the enzymatic mechanisms involved in TC biosynthesis have signifi cantly contributed to the low success of such biosynthetic engineering eff orts. However, new opportunities in TC drug development have arisen thanks to a signifi cant progress in the development of aff ordable and versatile biosynthetic engineering and synthetic biology approaches, and, importantly, to a much deeper understanding of TC biosynthesis, mostly gained over the last two decades.

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Synthetic Biology of Antibiotic Production

Takano

Breitling

2014

Encyclopedia of Molecular Cell Biology and Molecular Medicine

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Heterologous Expression and Manipulation of Three Tetracycline Biosynthetic Pathways

Cited by 47 publications

References 34 publications

Physiology, Biochemistry, and Applications of F₄₂₀- and F_o-Dependent Redox Reactions

Physiology, Biochemistry, and Applications of F₄₂₀- and F_o-Dependent Redox Reactions

Biosynthesis of Oxytetracycline by Streptomyces rimosus: Past, Present and Future Directions in the Development of Tetracycline Antibiotics

Synthetic Biology of Antibiotic Production

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Heterologous Expression and Manipulation of Three Tetracycline Biosynthetic Pathways

Cited by 47 publications

References 34 publications

Physiology, Biochemistry, and Applications of F420- and Fo-Dependent Redox Reactions

Physiology, Biochemistry, and Applications of F420- and Fo-Dependent Redox Reactions

Biosynthesis of Oxytetracycline by Streptomyces rimosus: Past, Present and Future Directions in the Development of Tetracycline Antibiotics

Synthetic Biology of Antibiotic Production

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Physiology, Biochemistry, and Applications of F₄₂₀- and F_o-Dependent Redox Reactions

Physiology, Biochemistry, and Applications of F₄₂₀- and F_o-Dependent Redox Reactions