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Related Concept Videos

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...
Upstream Processing01:27

Upstream 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...

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Related Experiment Video

Updated: May 9, 2026

From a Natural Product to Its Biosynthetic Gene Cluster: A Demonstration Using Polyketomycin from Streptomyces diastatochromogenes T&#252;6028
09:08

From a Natural Product to Its Biosynthetic Gene Cluster: A Demonstration Using Polyketomycin from Streptomyces diastatochromogenes Tü6028

Published on: January 13, 2017

The PreKit platform: Cryptic gene clusters activation and high-titer compound production.

Zhongyu Chen1, Yelin Duan1, Lei Liu1

  • 1State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory on Metabolic & Developmental Sciences, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China.

Synthetic and Systems Biotechnology
|May 8, 2026
PubMed
Summary
This summary is machine-generated.

Researchers developed a new platform to activate silent biosynthetic gene clusters (BGCs) for drug discovery. This method successfully produced novel polyketide compounds with antibacterial activity, enhancing drug development pipelines.

Keywords:
Cryptic gene clusters activationHeterologous expressionHigh-titer compound productionPreKitToolkit

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A High-throughput Automated Platform for the Development of Manufacturing Cell Lines for Protein Therapeutics
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A High-throughput Automated Platform for the Development of Manufacturing Cell Lines for Protein Therapeutics

Published on: September 22, 2011

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Last Updated: May 9, 2026

From a Natural Product to Its Biosynthetic Gene Cluster: A Demonstration Using Polyketomycin from Streptomyces diastatochromogenes T&#252;6028
09:08

From a Natural Product to Its Biosynthetic Gene Cluster: A Demonstration Using Polyketomycin from Streptomyces diastatochromogenes Tü6028

Published on: January 13, 2017

A High-throughput Automated Platform for the Development of Manufacturing Cell Lines for Protein Therapeutics
07:48

A High-throughput Automated Platform for the Development of Manufacturing Cell Lines for Protein Therapeutics

Published on: September 22, 2011

Area of Science:

  • Synthetic biology
  • Natural product drug discovery
  • Metabolic engineering

Background:

  • Genome mining of biosynthetic gene clusters (BGCs) is crucial for identifying novel drug scaffolds.
  • Many microbial BGCs remain silent under laboratory conditions, hindering natural product discovery.
  • Activating silent BGCs via promoter engineering and heterologous expression faces challenges like host-promoter-media incompatibilities.

Purpose of the Study:

  • To develop a streamlined platform for activating silent BGCs by overcoming multi-factor incompatibilities.
  • To create a plug-and-play promoter toolkit for efficient BGC activation.
  • To enhance the production of novel secondary metabolites and evaluate their bioactivity.

Main Methods:

  • Developed a platform integrating a promoter library with an indC-based reporter system for combinatorial screening.
  • Applied the platform and a plug-and-play promoter toolkit to activate a silent type II polyketide synthase (PKS) gene cluster (spa).
  • Integrated a non-carboxylative malonyl-CoA (NCM) pathway into S. lividans to enhance precursor supply.

Main Results:

  • Successfully activated the silent spa BGC, yielding new aromatic polyketides, strepanthenes A (1a) and streptoketide C (1b).
  • Achieved a 3.6-fold and 3.3-fold increase in titers for compounds 1a and 1b, respectively, after NCM pathway integration.
  • Compound 1a demonstrated antibacterial activity against S. aureus and E. faecalis (MIC: 4 μg mL-1).

Conclusions:

  • The developed platform and toolkit offer a versatile and efficient strategy for activating silent BGCs.
  • This approach significantly improves secondary metabolite production through combinatorial screening and precursor enhancement.
  • The discovery of bioactive compound 1a highlights the potential of this method for novel drug discovery.