Regulation of antibiotic biosynthesis in actinomycetes: Perspectives and challenges

Wei, Junhong; He, Lang; Niu, Guoqing

doi:10.1016/j.synbio.2018.10.005

Cited by 46 publications

(33 citation statements)

References 125 publications

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“…Hormone-like signaling molecules are a group of small diffusible signaling molecules that can elicit antibiotic production and/or induce morphological differentiation at nanomolar concentrations. Typically, a hormone-like signaling molecule binds to its specific receptor, and exerts regulatory function through regulators at different hierarchical levels, including global regulators, pleiotropic regulators, and cluster-situated regulators (CSRs) (Liu et al, 2013;Niu and Tan, 2015;Wei et al, 2018). The most-studied regulatory system is the A-factor cascade that involves the signaling molecule A-factor and its receptor ArpA necessary for streptomycin and grixazone production in Streptomyces griseus (Horinouchi, 2007;Horinouchi and Beppu, 2007).…”

Section: Introductionmentioning

confidence: 99%

Regulation of Antibiotic Production by Signaling Molecules in Streptomyces

Kong

Wang

et al. 2019

Front. Microbiol.

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The genus Streptomyces is a unique subgroup of actinomycetes bacteria that are well-known as prolific producers of antibiotics and many other bioactive secondary metabolites. Various environmental and physiological signals affect the onset and level of production of each antibiotic. Here we highlight recent findings on the regulation of antibiotic biosynthesis in Streptomyces by signaling molecules, with special focus on autoregulators such as hormone-like signaling molecules and antibiotics themselves. Hormone-like signaling molecules are a group of small diffusible signaling molecules that interact with specific receptor proteins to initiate complex regulatory cascades of antibiotic biosynthesis. Antibiotics and their biosynthetic intermediates can also serve as autoregulators to fine-tune their own biosynthesis or cross-regulators of disparate biosynthetic pathways. Advances in understanding of signaling molecules-mediated regulation of antibiotic production in Streptomyces may aid the discovery of new signaling molecules and their use in eliciting silent antibiotic biosynthetic pathways in a wide range of actinomycetes.

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Section: Introductionmentioning

confidence: 99%

Regulation of Antibiotic Production by Signaling Molecules in Streptomyces

Kong

Wang

et al. 2019

Front. Microbiol.

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“…The most known and used constitutive systems are ermE *p [ 110 ], SF14 *p [ 111 ], kasO *p [ 112 ]. Dynamic regulation of gene or pathway expression can be achieved by applying metabolite-responsive promoters such as the thiostrepton-( tipA *p) [ 113 ] or ε-caprolactam inducible promoter ( nitA* p) [ 114 ], quorum sensing (operator/repressor) systems [ 115 , 116 ] (e.g., tetO –TetR [ 117 ], gylR and gylP1/P2 [ 85 , 118 ]), pleiotropic/pathway-specific regulators (e.g., SARP family, TetR family) [ 119 , 120 , 121 , 122 ], and protein/RNA-based biosensors (e.g., TetR-based biosensors) [ 123 , 124 , 125 , 126 , 127 , 128 ]. Some of these concepts were initially developed in E. coli and/or Saccharomyces cerevisiae and later adapted to actinomycetes.…”

Section: Genetic Engineering Of Actinomycetesmentioning

confidence: 99%

An Update on Molecular Tools for Genetic Engineering of Actinomycetes—The Source of Important Antibiotics and Other Valuable Compounds

2020

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The first antibiotic-producing actinomycete (Streptomyces antibioticus) was described by Waksman and Woodruff in 1940. This discovery initiated the “actinomycetes era”, in which several species were identified and demonstrated to be a great source of bioactive compounds. However, the remarkable group of microorganisms and their potential for the production of bioactive agents were only partially exploited. This is caused by the fact that the growth of many actinomycetes cannot be reproduced on artificial media at laboratory conditions. In addition, sequencing, genome mining and bioactivity screening disclosed that numerous biosynthetic gene clusters (BGCs), encoded in actinomycetes genomes are not expressed and thus, the respective potential products remain uncharacterized. Therefore, a lot of effort was put into the development of technologies that facilitate the access to actinomycetes genomes and activation of their biosynthetic pathways. In this review, we mainly focus on molecular tools and methods for genetic engineering of actinomycetes that have emerged in the field in the past five years (2015–2020). In addition, we highlight examples of successful application of the recently developed technologies in genetic engineering of actinomycetes for activation and/or improvement of the biosynthesis of secondary metabolites.

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“…Subsequently, the ends of the aerial hyphae tips differentiate into unigenomic spores that will disseminate in the environment. In solid-grown cultures, the production of secondary metabolites usually coincides with the onset of morphological differentiation indicating the existence of regulatory features common to these two processes (Chater, 2006;Liu et al, 2013;Wei et al, 2018). Regulatory cascades triggered by the sensing of extracellular and/or intracellular signals are involved in the control of the developmental program (Pereira et al, 2011).…”

Section: Introductionmentioning

confidence: 99%