J. Adv. Biomed. & Pharm. Sci. J. Adv. Biomed. & Pharm. Sci. 6 (2023) 36 - 48 Biodiversity of Actinomycetes and Their Secondary Metabolites: A Comprehensive Review Sadaf khan 1 , Shanzeba 1 , Aisha gul 1 , Saqlain Jehan 1 , Zahid Khan 2 , Javaria saeed 3 , Ramiz Raza Shirazi 4 , Abdur Raziq 5 , Muhammad Waseem Khan 6 , Hayat Ullah 5* Institute of Biotechnology and Genetic Engineering University, The University of Agriculture Peshawar, Pakistan 1 Department of Zoology, University of Swabi, Khyber Pakhtunkhwa, Pakistan 2 Lahore, Pakistan Institute of Industrial Biotechnology, Government college university 3 Pakistan , Department of Chemistry, Government College University Faisalabad 4 amp; Biotechnology, Faculty of Life Science, Government College University Faisalabad, Pakistan. Department of Bioinformatics & 5 Department of Biotechnology, Faculty of Life Sciences, Balochistan University of Information Technology Engineering and 6 Management Sciences, Quetta, Pakistan Received: September 8, 2022; revised: November 15, 2022; accepted: November 17, 2022 Abstract Background: Among prokaryotes, Actinomycetes are one of the most explored microorganism due to their capability of novel bioactive secondary metabolites production. Actinomycetes secondary metabolites are known for their role in different cellular, physiological and biological processes. Main body: Actinomycetes are most widely distributed in natural ecosystem habitats such as soil, hypersaline soil, rhizosphere soil, freshwater, limestone, volcanic cave, marine sediments, sponges, and desert. Actinomycetes bioactive secondary metabolites most important features are that they have specific microbial producers, diverse bioactivities and unique chemical structures. Some important antibiotics produced by actinomycetes are actinomycetin, mycetin, micromonosporin and from actinomyces are lysozyme, actinomycin, streptothricin, proactinomycin and streptomycin. These antibiotics differ greatly in their structure, antimicrobial and toxicity properties. Actinomycetes secondary metabolites include spirotetronate, quinones, lactams, aminoglycosides, β -lactams, diketones, aromatic ketones, ansamycin, glycopeptides, lactones, Tetracenediones, anthracyclines, macrolides, fattiviracins, polyenes and tetracyclines, natural polycyclic polyketide. Conclusion: This review study summarized that Actinomycetes are naturally distributed species found in diverse environments. It is assumed that actinomycetes species found in extreme conditions have the capability to produce novel bioactive secondary metabolites that remain unexplored yet. Keywords Actinomycetes, Antibiotics, Biodiversity of Actinomycetes, Secondary Metabolites 1. Introduction Actinomycetes are Gram-positive filamentous bacteria and their genome contains high GC (guanine and cytosine) content. Actinomycetes are ubiquitously found in both aquatic and terrestrial ecosystems [1]. Many actinomycetes have mycelial lifestyle and undergo complex morphological differentiation. Actinomycetes produce about two-thirds of all antibiotics available in the market. Bio-active secondary metabolites produced by actinomycetes are used as antibiotics, antifungal, anticholesterol, antiprotozoal, antiviral, anticancer, antihelminth immunosuppressant and as a single cell protein [2]. Actinomycetes are commonly found in natural environment and have an important role in biodegradation of organic matter [3]. Actinomycetes have prominent value in their diversity, their secondary metabolites have the capability of bioactive molecules which act as antibiotics, enzymes and immunosuppressive and antitumor agents and produced half of the available antibiotics on the market. For the past fifty years, due to huge antibiotic- producing sources, efforts have been focused on actinomycetes for the production of novel antibiotics [2,4]. Professor Alexander Fleming in 1928, most fortunate discovered antibiotics by chance in London, Staphylococci strain inoculated on agar left on his workbench, after a while, he noticed that a mold colony had contaminated the plate but around mold colonies there was no bacterial growth observed [5]. After observation, the suppressing bacterial growth was found and named as penicillin. After successful discovery, an extensive search started among other microbes for the production of such bio-active chemical compounds. During the last two decades, the most important groups of antibiotics that were discovered are tetracycline and macrolides [6]. Actinomycetes produce various bio-active compounds such as antibiotics, enzyme inhibitors and hydrolytic enzymes which are resistant to nutrient stress and desiccation by producing spores [7]. Actinobacteria play diverse roles in their associations with various higher organisms. Some Actinobacteria species and insects develop a naturally symbiotic relationship, where bacteria are formed in anatomical compartments while attine ants have symbiotic relation with fungi Leucoagaricus gongylophorus and these ants acquire Actinobacteria for useful antibiotics for controlling fungal counterparts. A similar relationship was found Journal of Advanced Biomedical and Pharmaceutical Sciences Journal Homepage: http://jabps.journals.ekb.eg * Correspondence: Hayat Ullah Tel.: 00923155655677 Email Address: hayatullah22@gcuf.edu.pk