Iteratively improving natamycin production in Streptomyces gilvosporeus by a large operon-reporter based strategy

Wang, Yemin; Tao, Zhengsheng; Zheng, Hualiang; Zhang, Fei; Long, Qingshan; Deng, Zixin; Tao, Meifeng

doi:10.1016/j.ymben.2016.10.005

Cited by 27 publications

(21 citation statements)

References 38 publications

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“…RGMS was initially developed for industrial strain improvement purposes by taking advantage of the correlation between increased transcription levels from the target BGC and product yields. The method has been used to improve production of lovastatin [ 198 ], clavulanic acid [ 199 ] and natamycin [ 200 ] in Aspergillus terreus , S. clavuligerus and S. gilvosporeus , respectively. In addition, the methodology has also been successfully carried out in combination with ribosome engineering, through exposure to streptomycin, to achieve over-production of daptomycin in S. roseosporus NRRL11379 [ 201 ].…”

Section: Strategies For the Activation Of Unknown Metabolic Pathwaysmentioning

confidence: 99%

Activation of microbial secondary metabolic pathways: Avenues and challenges

Baral

Akhgari

Metsä‐Ketelä

2018

Synthetic and Systems Biotechnology

166

146

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Microbial natural products are a tremendous source of new bioactive chemical entities for drug discovery. Next generation sequencing has revealed an unprecedented genomic potential for production of secondary metabolites by diverse micro-organisms found in the environment and in the microbiota. Genome mining has further led to the discovery of numerous uncharacterized ‘cryptic’ metabolic pathways in the classical producers of natural products such as Actinobacteria and fungi. These biosynthetic gene clusters may code for improved biologically active metabolites, but harnessing the full genetic potential has been hindered by the observation that many of the pathways are ‘silent’ under laboratory conditions. Here we provide an overview of the various biotechnological methodologies, which can be divided to pleiotropic, biosynthetic gene cluster specific, and targeted genome-wide approaches that have been developed for the awakening of microbial secondary metabolic pathways.

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Section: Strategies For the Activation Of Unknown Metabolic Pathwaysmentioning

confidence: 99%

Activation of microbial secondary metabolic pathways: Avenues and challenges

Baral

Akhgari

Metsä‐Ketelä

2018

Synthetic and Systems Biotechnology

166

146

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“…In this study a final titer of 4.0 g/L natamycin was achieved. Natamycin production in the natural producer Streptomyces gilvosporeus was improved by coupling the expression of the natamycin biosynthetic gene cluster to the expression of a kanamycin resistance gene (Wang et al, 2016 ). After seven iterative rounds of mutagenesis and selection for increased kanamycin resistance a strain producing 14.4 g/L natamycin was obtained.…”

Section: Metabolic Engineering For the Microbial Production Of Food Amentioning

confidence: 99%

Engineered Microorganisms for the Production of Food Additives Approved by the European Union—A Systematic Analysis

Kallscheuer

2018

Front. Microbiol.

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In the 1950s, the idea of a single harmonized list of food additives for the European Union arose. Already in 1962, the E-classification system, a robust food safety system intended to protect consumers from possible food-related risks, was introduced. Initially, it was restricted to colorants, but at later stages also preservatives, antioxidants, emulsifiers, stabilizers, thickeners, gelling agents, sweeteners, and flavorings were included. Currently, the list of substances authorized by the European Food Safety Authority (EFSA) (referred to as “E numbers”) comprises 316 natural or artificial substances including small organic molecules, metals, salts, but also more complex compounds such as plant extracts and polymers. Low overall concentrations of such compounds in natural producers due to inherent regulation mechanisms or production processes based on non-regenerative carbon sources led to an increasing interest in establishing more reliable and sustainable production platforms. In this context, microorganisms have received significant attention as alternative sources providing access to these compounds. Scientific advancements in the fields of molecular biology and genetic engineering opened the door toward using engineered microorganisms for overproduction of metabolites of their carbon metabolism such as carboxylic acids and amino acids. In addition, entire pathways, e.g., of plant origin, were functionally introduced into microorganisms, which holds the promise to get access to an even broader range of accessible products. The aim of this review article is to give a systematic overview on current efforts during construction and application of microbial cell factories for the production of food additives listed in the EU “E numbers” catalog. The review is focused on metabolic engineering strategies of industrially relevant production hosts also discussing current bottlenecks in the underlying metabolic pathways and how they can be addressed in the future.

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“…Studies showed that the natamycin biosynthesis gene clusters in S. natalensis and S. chattanoogensis have high similarity, and both include five large polyketide synthase (PKS) genes and dozens of genes for tailoring enzymes, transport, and regulation ( 9 , 10 ). Although the natamycin biosynthesis gene cluster from S. gilvosporeus Ins1 has been sequenced ( 11 ), no genome sequence of S. gilvosporeus has been reported. Due to the considerable commercial value of natamycin, we present here the first complete genome sequence and genomic features of S. gilvosporeus F607, a high-natamycin-producing industrial strain, which was developed from ATCC 13326 by various mutagens and collected by our laboratory.…”

Section: Genome Announcementmentioning

confidence: 99%

Complete Genome Sequence of the High-Natamycin-Producing Strain Streptomyces gilvosporeus F607

Zong

Zhong

et al. 2018

Genome Announc

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Streptomyces gilvosporeus strain F607 is a producer of high levels of natamycin used in the fermentation industry. In this study, the complete genome sequence of strain F607 was determined. This genome sequence provides a basis for understanding natamycin biosynthesis and regulation in a high-natamycin-producing strain and will aid in the development of useful strategies for improving industrial strains.

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Iteratively improving natamycin production in Streptomyces gilvosporeus by a large operon-reporter based strategy

Cited by 27 publications

References 38 publications

Activation of microbial secondary metabolic pathways: Avenues and challenges

Activation of microbial secondary metabolic pathways: Avenues and challenges

Engineered Microorganisms for the Production of Food Additives Approved by the European Union—A Systematic Analysis

Complete Genome Sequence of the High-Natamycin-Producing Strain Streptomyces gilvosporeus F607

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