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Amino Acid Biosynthetic Pathways01:29

Amino Acid Biosynthetic Pathways

Amino acid biosynthesis is essential for cell growth, protein synthesis, and metabolic regulation. Cells generate essential and non-essential amino acids from metabolic intermediates to sustain vital biological functions. These intermediates originate from key metabolic pathways: glycolysis, the tricarboxylic acid (TCA) cycle, and the pentose phosphate pathway. Important precursors include α-ketoglutarate, pyruvate, oxaloacetate, phosphoenolpyruvate, and erythrose-4-phosphate, which provide...
Biosynthesis in Bacteria01:24

Biosynthesis in Bacteria

Biosynthesis in bacteria is a fundamental anabolic process that generates essential macromolecules, including proteins, nucleic acids, lipids, and polysaccharides. These macromolecules are critical for cellular growth, replication, and function. The process is tightly regulated and energetically linked to catabolic pathways to ensure optimal resource utilization.Biosynthetic pathways begin with precursor metabolites such as pyruvate, acetyl-CoA, and glucose-6-phosphate derived from glycolysis,...
Synthetic Biology02:55

Synthetic Biology

Synthetic biology is an interdisciplinary science that involves using principles from disciplines such as engineering, molecular biology, cell biology, and systems biology. It involves remodeling existing organisms from nature or constructing completely new synthetic organisms for applications such as protein or enzyme production, bioremediation, value-added macromolecule production, and the addition of desirable traits to crops, to name a few.
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Production of Pharmaceuticals01:30

Production of Pharmaceuticals

Industrial insulin production uses genetically engineered E. coli expressing a proinsulin gene controlled by a tryptophan promoter and containing a methionine linker for later cleavage. The cells also carry ampicillin resistance for selective growth. Seed cultures are stored at −80 °C and production begins by thawing a small amount to inoculate starter cultures, which are progressively scaled to a 50,000-L bioreactor. In the bioreactor, E. coli grow in nutrient-rich media under sterile, tightly...
Production of Antibiotics01:27

Production of Antibiotics

Penicillin, one of the earliest and most widely used antibiotics, is produced industrially by the filamentous fungus Penicillium chrysogenum. Large stirred-tank bioreactors ranging from tens to hundreds of thousands of liters maintain tightly controlled temperature, pH, and dissolved oxygen conditions to support fungal metabolism and maximize antibiotic yield. Penicillin is a secondary metabolite, synthesized primarily during the stationary growth phase, which requires a carefully managed...
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Mass Spectrometry-Guided Genome Mining as a Tool to Uncover Novel Natural Products
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Mass Spectrometry-Guided Genome Mining as a Tool to Uncover Novel Natural Products

Published on: March 12, 2020

Mining and engineering natural-product biosynthetic pathways.

Barrie Wilkinson1, Jason Micklefield

  • 1Biotica, Chesterford Research Park, Little Chesterford, Essex CB10 1XL, UK. barrie.wilkinson@biotica.com

Nature Chemical Biology
|June 20, 2007
PubMed
Summary

Natural products are vital for developing new therapeutics and biological tools. Genome mining and genetic engineering unlock novel compounds by expressing complex biosynthetic gene clusters in new hosts.

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Mass Spectrometry-Guided Genome Mining as a Tool to Uncover Novel Natural Products
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From a Natural Product to Its Biosynthetic Gene Cluster: A Demonstration Using Polyketomycin from Streptomyces diastatochromogenes T&#252;6028
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From a Natural Product to Its Biosynthetic Gene Cluster: A Demonstration Using Polyketomycin from Streptomyces diastatochromogenes Tü6028

Published on: January 13, 2017

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Natural Products Chemistry

Background:

  • Natural products are crucial for drug discovery and as tools for biological research.
  • Accessing diverse natural product structures is limited by current exploitation methods.
  • Chemical genetics and high-throughput screening increase the value of natural products.

Purpose of the Study:

  • To explore unexploited natural product structural diversity.
  • To enhance the cloning and expression of large, cryptic biosynthetic gene clusters.
  • To advance lead optimization and diversification of natural product libraries.

Main Methods:

  • Genome mining and microbial metagenomic approaches to identify gene clusters.
  • Recombineering and genetic tools for cloning and heterologous expression.
  • Combinatorial biosynthetic engineering for structural diversification.

Main Results:

  • Successful cloning and expression of previously intractable biosynthetic gene clusters.
  • Generation of diverse natural product libraries through engineering.
  • Recent structural data on fatty acid synthases aids prediction of related enzyme complexes.

Conclusions:

  • Genome mining and genetic tools are powerful for accessing novel natural product diversity.
  • Combinatorial biosynthetic engineering is essential for drug lead optimization.
  • Understanding enzyme structure and function is key to rationally redesigning biosynthetic pathways.