Abstract

Microorganisms produce a range of chemical substances representing a vast diversity of fascinating molecular architectures not available in any other system. Among them, Streptomyces are frequently used to produce useful enzymes and a wide variety of secondary metabolites with potential biological activities. Streptomyces are preferred over other microorganisms for producing more than half of the clinically useful naturally originating pharmaceuticals. However, these compounds are usually produced in very low amounts (or not at all) under typical laboratory conditions. Despite the superiority of Streptomyces, they still lack well documented genetic information and a large number of in-depth molecular biological tools for strain improvement. Previous attempts to produce high yielding strains required selection of the genetic material through classical mutagenesis for commercial production of secondary metabolites, optimizing culture conditions, and random selection. However, a profound effect on the strategy for strain development has occurred with the recent advancement of whole-genome sequencing, systems biology, and genetic engineering. In this review, we demonstrate a few of the major issues related to the potential of “-omics” technology (genomics, transcriptomics, proteomics, and metabolomics) for improving streptomycetes as an intelligent chemical factory for enhancing the production of useful bioactive compounds.

Highlights

  • Natural products are chemical compounds with pharmacological characteristics produced by living organisms that can be utilized during pharmaceutical drug discovery, agriculture, and in the food industry

  • Microbial fermentation is widely applied to industrially produce these valuable compounds. These compounds are produced in very low amounts by natural strains under typical laboratory conditions to meet commercial requirements, demonstrating the need for heterologous expression of these biosynthetic gene clusters

  • They are Gram-positive mycelial soil bacteria containing about 70% G-C DNA content and undergo a complex process of morphological development that usually involves secondary metabolite biosynthesis under depleted nutrient conditions [6]

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Summary

Introduction

Natural products are chemical compounds with pharmacological characteristics produced by living organisms that can be utilized during pharmaceutical drug discovery, agriculture, and in the food industry. Of the thousands of secondary metabolites documented, more than half are produced by Streptomyces (antibiotics, antitumor agents, immunosuppressants, antihelminthics, antifungals, herbicides, and insecticides) and have offered decades of interest to industry and academia [2, 3] (Table 1) Many of these secondary metabolites function as signaling molecules to control the metabolism of their own producer [4]. Responsible for secondary metabolite production is termed a biosynthetic gene cluster, which encompasses biosynthetic enzymes, resistance determinants, and regulatory proteins The use of these cryptic microbial secondary metabolic processes has attracted the attention of synthetic microbiologists who exploit recent advances in DNA sequencing and synthesis procedures to achieve unprecedented control over metabolic pathways. We conclude the paper by highlighting the future perspectives of recent technological advances yet to be applied to Streptomyces species for further stain improvement

Engineered Metabolic Networks
Engineered Genomics
Engineered Proteomics
Engineered Transcriptomics
Findings
Future Perspectives
Full Text
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