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      New Dimensions of Research on Actinomycetes: Quest for Next Generation Antibiotics

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          Abstract

          Starting with the discovery of streptomycin, the promise of natural products research on actinomycetes has been captivating researchers and offered an array of life-saving antibiotics. However, most of the actinomycetes have received a little attention of researchers beyond isolation and activity screening. Noticeable gaps in genomic information and associated biosynthetic potential of actinomycetes are mainly the reasons for this situation, which has led to a decline in the discovery rate of novel antibiotics. Recent insights gained from genome mining have revealed a massive existence of previously unrecognized biosynthetic potential in actinomycetes. Successive developments in next-generation sequencing, genome editing, analytical separation and high-resolution spectroscopic methods have reinvigorated interest on such actinomycetes and opened new avenues for the discovery of natural and natural-inspired antibiotics. This article describes the new dimensions that have driven the ongoing resurgence of research on actinomycetes with historical background since the commencement in 1940, for the attention of worldwide researchers. Coupled with increasing advancement in molecular and analytical tools and techniques, the discovery of next-generation antibiotics could be possible by revisiting the untapped potential of actinomycetes from different natural sources.

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          Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2).

          Streptomyces coelicolor is a representative of the group of soil-dwelling, filamentous bacteria responsible for producing most natural antibiotics used in human and veterinary medicine. Here we report the 8,667,507 base pair linear chromosome of this organism, containing the largest number of genes so far discovered in a bacterium. The 7,825 predicted genes include more than 20 clusters coding for known or predicted secondary metabolites. The genome contains an unprecedented proportion of regulatory genes, predominantly those likely to be involved in responses to external stimuli and stresses, and many duplicated gene sets that may represent 'tissue-specific' isoforms operating in different phases of colonial development, a unique situation for a bacterium. An ancient synteny was revealed between the central 'core' of the chromosome and the whole chromosome of pathogens Mycobacterium tuberculosis and Corynebacterium diphtheriae. The genome sequence will greatly increase our understanding of microbial life in the soil as well as aiding the generation of new drug candidates by genetic engineering.
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            Thoughts and facts about antibiotics: where we are now and where we are heading.

            The declining trends in microbial metabolite and natural products research and the refocusing of this research area are discussed. Renewing natural products research requires inexhaustible natural resources, as well as new genetic techniques and microbial sources, including endophytic microbes. The numbers of known bioactive metabolites are summarized according to their microbiological origin, biological activities and chemical structures. Synthetic and natural product-based libraries are also compared. Importantly, the wide range of microbial metabolite bioactivities, future trends and the importance of prioritizing natural products over synthetic compounds are emphasized.
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              Microbial drug discovery: 80 years of progress

              Microbes have made a phenomenal contribution to the health and well-being of people throughout the world. In addition to producing many primary metabolites, such as amino acids, vitamins and nucleotides, they are capable of making secondary metabolites, which constitute half of the pharmaceuticals on the market today and provide agriculture with many essential products. This review centers on these beneficial secondary metabolites, the discovery of which goes back 80 years to the time when penicillin was discovered by Alexander Fleming.
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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                19 August 2016
                2016
                : 7
                : 1295
                Affiliations
                [1] 1Marine Biotechnology and Ecology Division, CSIR – Central Salt and Marine Chemicals Research Institute Bhavnagar, India
                [2] 2Academy of Scientific and Innovative Research (AcSIR), Council of Scientific and Industrial Research New Delhi, India
                Author notes

                Edited by: Jem Stach, Newcastle University, UK

                Reviewed by: Nicholas Allenby, Demuris Ltd, UK; Osmar Nascimento Silva, Universidade Católica Dom Bosco, Brazil

                *Correspondence: Bhavanath Jha, bjha@ 123456csmcri.org Polpass Arul Jose, arulmku@ 123456gmail.com

                This article was submitted to Antimicrobials, Resistance and Chemotherapy, a section of the journal Frontiers in Microbiology

                Article
                10.3389/fmicb.2016.01295
                4990552
                010d934d-b305-4f4e-bd32-07b286edad81
                Copyright © 2016 Jose and Jha.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 21 May 2016
                : 05 August 2016
                Page count
                Figures: 1, Tables: 0, Equations: 0, References: 28, Pages: 5, Words: 0
                Funding
                Funded by: Council of Scientific and Industrial Research 10.13039/501100001412
                Award ID: BSC0106-BioprosPR, HRDG/CSIR-Nehru PDF LS/EMR-I/01/2015
                Categories
                Microbiology
                Perspective

                Microbiology & Virology
                actinomycetes,natural products,antibiotics,drug discovery,genomics,metabolomics

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