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Epigenetic modification, co-culture and genomic methods for natural product discovery

文献类型： 外文期刊

作者： Akone, Sergi Herve 1 ; Pham, Cong-Dat 2 ; Chen, Huiqin 3 ; Ola, Antonius R. B. 4 ; Ntie-Kang, Fidele 5 ; Proksch, Peter 8 ;

作者机构： 1.Univ Douala, Dept Chem, Fac Sci, POB 24157, Douala, Cameroon

2.Kyoto Prefectural Univ Med, Dept Chem, Sakyo Ku, 1-5 Shimogamohangi Cho, Kyoto 6060823, Japan

3.Chinese Acad Trop Agr Sci, Inst Trop Biosci & Biotechnol, Haikou 571101, Hainan, Peoples R China

4.Nusa Cendana Univ, Chem Dept, Kupang, Indonesia

5.Univ Buea, Dept Chem, Fac Sci, POB 63, Buea, Cameroon

6.Martin Luther Univ Halle Wittenberg, Dept Pharmaceut Chem, Wolfgang Langenbeck Str 4, D-06120 Halle, Saale, Germany

7.Univ Chem & Technol Prague, Dept Informat & Chem, Tech 5, Prague 16628 6, Czech Republic

8.Heinrich Heine Univ Dusseldorf, Inst Pharmaceut Biol & Biotechnol, Univ Str 1,Geb 26-23, D-40225 Dusseldorf, Germany

关键词： fungi; bacteria; epigenetic modification; co-culture; genomics; silent genes

期刊名称：PHYSICAL SCIENCES REVIEWS

ISSN： 2365-6581

年卷期： 2019 年 4 卷 4 期

页码：

收录情况： SCI

摘要： Fungi and bacteria are encountered in many habitats where they live in complex communities interacting with one another mainly by producing secondary metabolites, which are organic compounds that are not directly involved in the normal growth, development, or reproduction of the organism. These organisms appear as a promising source for the discovery of novel bioactive natural products that may find their application in medicine. However, the production of secondary metabolites by those organisms when cultured axenically is limited as only a subset of biosynthetic genes is expressed under standard laboratory conditions leading to the search of new methods for the activation of the silent genes including epigenetic modification and co-cultivation. Biosynthetic gene clusters which produce secondary metabolites are known to be present in a heterochromatin state in which the transcription of constitutive genes is usually regulated by epigenetic modification including DNA methylation and histone deacetylation. Therefore, small-molecule epigenetic modifiers which promote changes in the structure of chromatin could control the expression of silent genes and may be rationally employed for the discovery of novel bioactive compounds. Co-cultivation, which is also known as mixed-fermentation, usually implies two or more microorganisms in the same medium in which the resulting competition is known to enhance the production of constitutively present compounds and/or to lead to the induction of cryptic metabolites that were not detected in axenic cultures of the considered axenic microorganism. Genomic strategies could help to identify biosynthetic gene clusters in fungal genomes and link them to their products by the means of novel algorithms as well as integrative pan-genomic approaches. Despite that all these techniques are still in their infancy, they appear as promising sources for the discovery of new bioactive compounds. This chapter presents recent ecological techniques for the discovery of new secondary metabolites that might find application in medicine.

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