Molecular cloning and functional characterization of an ATP-binding cassette transporter OtrC from Streptomyces rimosus

Yu, Ling; Yan, Xiangyun; Wang, Long; Chu, Ju; Zhuang, Yingping; Zhang, Siliang; Guo, Meijin

doi:10.1186/1472-6750-12-52

Cited by 29 publications

(18 citation statements)

References 32 publications

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“…For instance, S. rimosus encodes a third oxytetracycline resistance protein OtrC, which is an ABC transport protein. Although this gene is located outside of the oxytetracycline biosynthetic gene cluster, it has been shown to confer high level resistance of oxytetracycline when expressed heterologously in other bacteria (Yu et al, 2012). It is unclear why a third resistance mechanism is needed or whether it is in fact important for conferring resistance.…”

Section: Exceptions and Outliersmentioning

confidence: 99%

The expression of antibiotic resistance genes in antibiotic‐producing bacteria

Mak

Nodwell

2014

Molecular Microbiology

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SummaryAntibiotic-producing bacteria encode antibiotic resistance genes that protect them from the biologically active molecules that they produce. The expression of these genes needs to occur in a timely manner: either in advance of or concomitantly with biosynthesis. It appears that there have been at least two general solutions to this problem. In many cases, the expression of resistance genes is tightly linked to that of antibiotic biosynthetic genes. In others, the resistance genes can be induced by their cognate antibiotics or by intermediate molecules from their biosynthetic pathways. The regulatory mechanisms that couple resistance to antibiotic biosynthesis are mechanistically diverse and potentially relevant to the origins of clinical antibiotic resistance.

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Section: Exceptions and Outliersmentioning

confidence: 99%

The expression of antibiotic resistance genes in antibiotic‐producing bacteria

Mak

Nodwell

2014

Molecular Microbiology

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“…The overexpression of efflux transporters can extrude terpenes, biofuels, and antibiotics . However, it was difficult and time‐consuming to select hundreds and thousands of transporters for some specific compound to know whether it will efflux the target compound or not as there are thousands of transport proteins in different organisms .…”

Section: Discussionmentioning

confidence: 99%

“…Transporter engineering strategies generally enhance the culture vitality and the total yields due to which wild strains can withstand toxic compounds . The overexpression of the efflux transporters can extrude terpenes, biofuels, and antibiotics . However, it is complicated and time‐consuming to select hundreds and thousands of transporters for some specific compound to know whether it will efflux the target compound or not as there are thousands of transport proteins in different organisms.…”

Section: Introductionmentioning

confidence: 99%

“…10 The overexpression of the efflux transporters can extrude terpenes, biofuels, and antibiotics. [12][13][14] However, it is complicated and time-consuming to select hundreds and thousands of transporters for some specific compound to know whether it will efflux the target compound or not as there are thousands of transport proteins in different organisms. To overcome this issue, computational approaches were utilized to explore the interactions of the target compound with the transport proteins for the possible efflux of -amyrin.…”

Section: Introductionmentioning

confidence: 99%

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Identification of effective membrane efflux transporters against β‐amyrin through molecular docking approach

Ahmed

Sehgal

Tahir

et al. 2019

J of Chemical Tech & Biotech

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BACKGROUND Metabolic engineering techniques in microorganisms can produce high‐value complex metabolites. However, this efficiency was frequently hampered by toxic‐compounds produced due to the engineering of foreign genes. Comparatively, to other strategies, the efflux transporter engineering strategy is efficient to create a pulling effect at the downstream of the biosynthetic pathway, generally enhancing the cultural vitality and the total production yields due to which wild strains can withstand toxic compounds. However, it was difficult to select hundreds of transporters for the possible efflux of β‐amyrin. Thus, in silico approaches were used to explore the binding sites of the transporters and identify the stable binding patterns of transporters for the possible efflux of β‐amyrin. RESULTS A total 111 transporters were shortlisted having the ability to transport different compounds. Molecular docking analyses elucidated that YajR, UraA, GlcPse, and LeuT, transporters have strong binding affinities against β‐amyrin having least binding energies of −13.6, −13.4, −12.2, and − 11.9 kcal/mol, respectively. CONCLUSION For the first time, it was observed that the mentioned top‐ranked transporters might be the better option to efflux β‐amyrin for being effectively bound within the enclosed active site. These novel findings based on computational docking analyses may be momentous to enhance the metabolites production in the microorganism. © 2019 Society of Chemical Industry

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“…Thus, the overall topology of the otrB-oxyTA1 region mirrors that found in Tn10, with the expression of the tetracycline effl ux pump being controlled by a divergent repressor (78,83). Finally, the otrC gene, which is not part of the otc gene cluster, is only ensuring a lower level of resistance against OTC (85). Yu et al (85) have presented evidence in their recent publication indicating that otrC encodes a protein with ATPase and multidrug effl ux activity.…”

Section: Regulation Of Tetracycline Biosynthesis and Genes Involved Imentioning

confidence: 99%

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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Molecular cloning and functional characterization of an ATP-binding cassette transporter OtrC from Streptomyces rimosus

Cited by 29 publications

References 32 publications

The expression of antibiotic resistance genes in antibiotic‐producing bacteria

The expression of antibiotic resistance genes in antibiotic‐producing bacteria

Identification of effective membrane efflux transporters against β‐amyrin through molecular docking approach

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

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