Related Experiment Video
Updated: May 23, 2026
09:08
From a Natural Product to Its Biosynthetic Gene Cluster: A Demonstration Using Polyketomycin from Streptomyces diastatochromogenes Tü6028
Published on: January 13, 2017
Bioengineering natural product biosynthetic pathways for therapeutic applications
Ming-Cheng Wu1, Brian Law, Barrie Wilkinson
1School of Chemistry and Manchester Interdisciplinary Biocentre, The University of Manchester, Manchester M1 7DN, UK.
Current Opinion in Biotechnology
|April 11, 2012
Summary
Next-generation sequencing reveals numerous microbial biosynthetic gene clusters. Bioengineering strategies are crucial for activating silent pathways and increasing natural product yields for therapeutic development.
Area of Science:
- Microbial genomics
- Natural product discovery
- Bioengineering
Background:
- Next-generation DNA sequencing has led to a surge in microbial genome data, uncovering many novel biosynthetic gene clusters.
- Most identified biosynthetic gene clusters are silent or yield low quantities of natural products, hindering drug development.
- Understanding enzyme mechanisms is key to unlocking these pathways.
Purpose of the Study:
- To review the latest bioengineering approaches for optimizing natural product yields.
- To explore strategies for increasing the structural diversity of natural product scaffolds.
- To facilitate the development of natural products for clinical applications.
Main Methods:
- Genomic data analysis to identify biosynthetic gene clusters.
- Bioengineering techniques to activate silent or low-yielding pathways.
- Enzyme mechanism studies to guide pathway re-programming.
Main Results:
- Identification of a vast number of new biosynthetic gene clusters.
- Development of methods to activate unproductive biosynthetic pathways.
- Creation of focused libraries of modified natural products with potentially enhanced properties.
Conclusions:
- Bioengineering offers powerful tools to overcome challenges in natural product drug discovery.
- Activating silent gene clusters and diversifying scaffolds are critical for future therapeutics.
- Optimizing yields and structural diversity are essential for clinical translation.
Related Concept Videos
02:55Synthetic 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.
Golden rice
Golden rice is a genetically modified...
Golden rice
Golden rice is a genetically modified...
01:24Biosynthesis 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,...
01:29Amino 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...
01:30Production 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...
01:29Microorganisms in Medicine and Therapeutics
Microorganisms play a fundamental role in vaccine development, gene therapy, and therapeutic production. Their biological properties are harnessed to advance medicine and public health. Beyond immunization, microorganisms contribute to gut health, antibiotic synthesis, and genetic disease treatment.Live Attenuated and Inactivated VaccinesLive attenuated vaccines, such as the measles, mumps, and rubella (MMR) vaccine, utilize weakened forms of pathogens to closely resemble natural infections.
01:27Upstream Processing
Upstream processing represents a critical phase in biomanufacturing, wherein biological systems such as microorganisms, mammalian cells, or insect cells are cultivated to produce therapeutic proteins, vaccines, enzymes, or other biologically derived products. This phase encompasses all steps from the selection and genetic manipulation of the production organism to the cultivation of cells in bioreactors under tightly controlled environmental conditions.Host Selection and Genetic OptimizationThe...