Recent advances in the discovery and combinatorial biosynthesis of microbial 14-membered macrolides and macrolactones

Park, Je Won; Yoon, Yeo Joon

doi:10.1007/s10295-018-2095-4

Cited by 11 publications

(13 citation statements)

References 70 publications

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“…The type I PKSs are multi-modular enzymes with non-iterative catalysis of one cycle of polyketide-chain elongation that are liable for consecutive condensation of activated coenzyme A (CoA) thioesters, including acetyl-CoA, propionyl-CoA, malonyl-CoA, or methylmalonyl-CoA. Each module minimally contains a set of functional domains, acyltransferase (AT), β-ketosynthase (KS), and acyl carrier protein (ACP) that are required for growing a polyketide chain and generating a β-ketoacyl-S-ACP intermediate [25,26]. In addition, the modules may also contain domains that consecutively modify the β-keto group to a hydroxyl group (ketoreductase, KR), a double bound (dehydrase, DH), and a single bond (enoyl reductase, ER) [26,27].…”

Section: Biosynthesis Challengesmentioning

confidence: 99%

Marine Macrolides to Tackle Antimicrobial Resistance of Mycobacterium tuberculosis

et al. 2022

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Tuberculosis has become a major health problem globally. This is worsened by the emergence of resistant strains of Mycobacterium tuberculosis showing ability to evade the effectiveness of the current antimycobacterial therapies. Therefore, the efforts carried out to explore new entities from many sources, including marine, are critical. This review summarizes several marine-derived macrolides that show promising activity against M. tuberculosis. We also provide information regarding the biosynthetic processes of marine macrolides, including the challenges that are usually experienced in this process. As most of the studies reporting the antimycobacterial activities of the listed marine macrolides are based on in vitro studies, the future direction should consider expanding the trials to in vivo and clinical trials. In addition, in silico studies should also be explored for a quick screening on marine macrolides with potent activities against mycobacterial infection. To sum up, macrolides derived from marine organisms might become therapeutical options for tackling antimycobacterial resistance of M. tuberculosis.

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Section: Biosynthesis Challengesmentioning

confidence: 99%

Marine Macrolides to Tackle Antimicrobial Resistance of Mycobacterium tuberculosis

et al. 2022

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“…However, Yuzawa et al identified the highly conserved boundaries and exhibited the feasibility of AT domain replacement in macrolides [96]. But the direct engineering of innate AT domain can be a more reliable alternative for varying the substrate ranges [97]. For example, the site-directed mutagenesis of AT domain and feeding of 2-propagylmalonyl-SNAC to S. erythraea (containing AT6 of DEBS mutated with Val295 to Ala) to generate 2-propargyl erythromycin [98].…”

Section: Metabolic Engineering Approaches In Actinomycetes For Macrolmentioning

confidence: 99%

Engineering actinomycetes for biosynthesis of macrolactone polyketides

2019

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Actinobacteria are characterized as the most prominent producer of natural products (NPs) with pharmaceutical importance. The production of NPs from these actinobacteria is associated with particular biosynthetic gene clusters (BGCs) in these microorganisms. The majority of these BGCs include polyketide synthase (PKS) or non-ribosomal peptide synthase (NRPS) or a combination of both PKS and NRPS. Macrolides compounds contain a core macro-lactone ring (aglycone) decorated with diverse functional groups in their chemical structures. The aglycon is generated by megaenzyme polyketide synthases (PKSs) from diverse acyl-CoA as precursor substrates. Further, post-PKS enzymes are responsible for allocating the structural diversity and functional characteristics for their biological activities. Macrolides are biologically important for their uses in therapeutics as antibiotics, anti-tumor agents, immunosuppressants, anti-parasites and many more. Thus, precise genetic/metabolic engineering of actinobacteria along with the application of various chemical/biological approaches have made it plausible for production of macrolides in industrial scale or generation of their novel derivatives with more effective biological properties. In this review, we have discussed versatile approaches for generating a wide range of macrolide structures by engineering the PKS and post-PKS cascades at either enzyme or cellular level in actinobacteria species, either the native or heterologous producer strains.

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“…Соединения с 14-, 15-или 16-членными лактонными кольцами включают широко известные антибактериальные лекарственные средства эритромицин, азитромицин и кларитромицин. Эритромицин (в состав которого входит 14-членное кольцо) был первым выделенным и идентифицированным макролидом [1]. С момента открытия эритромицина в 1952 г. был получен ряд других безопасных полусинтетических производных, которые в настоящее время используются в клинической практике.…”

Section: Introductionunclassified

Non-antimicrobial effects of macrolides: literature review

Skryabina¹,

Nikiforov²,

Shakhmardanov³

et al. 2021

Immunopathol Allergol Infectol

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The aim of this work is to review current publications on the non-antibacterial effects of macrolides. Macrolides are among the most widely prescribed broad-spectrum antibacterial drugs, especially in patients with respiratory infections. It is now recognized that drugs of this group, in particular azithromycin, also have an immunomodulatory effect, which leads to their therapeutic effect not only in infectious but in other chronic inflammatory diseases also. However, the frequent and prolonged use of macrolides in the treatment of respiratory tract diseases, and recently azithromycin in the treatment of COVID-19, has led to an increase in bacterial resistance to antibiotics of this group. Results: it was shown that one of the key aspects of the development of chronic inflammation of the respiratory tract (for instance, chronic obstructive pulmonary disease) is the loss of the protective epithelial barrier due to the effects of pathogens and pollutants. Azithromycin has been shown to enhance the barrier properties of airway epithelial cells over time, which makes an important contribution to its therapeutic effectiveness. The main non-antibacterial effects of macrolides are considered, which in the future can be applied in treatment of inflammatory diseases associated with airway epithelium damage.

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Recent advances in the discovery and combinatorial biosynthesis of microbial 14-membered macrolides and macrolactones

Cited by 11 publications

References 70 publications

Marine Macrolides to Tackle Antimicrobial Resistance of Mycobacterium tuberculosis

Marine Macrolides to Tackle Antimicrobial Resistance of Mycobacterium tuberculosis

Engineering actinomycetes for biosynthesis of macrolactone polyketides

Non-antimicrobial effects of macrolides: literature review

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