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Engineered polyketides: Synergy between protein and host level engineering.

Jesus F Barajas1, Jacquelyn M Blake-Hedges2, Constance B Bailey3,4

  • 1Department of Energy Agile BioFoundry, Emeryville, CA, USA.

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|January 11, 2018
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Summary
This summary is machine-generated.

Metabolic engineering uses modular polyketide synthases (PKSs) to create diverse compounds. Engineering these PKS systems offers new routes for producing valuable chemicals like medicines and fuels.

Keywords:
ACP, Acyl carrier proteinAT, AcyltransferaseCoL, CoA-LigaseCommodity chemicalDE, Dimerization elementDEBS, 6-deoxyerythronolide B synthaseDH, DehydrataseER, EnoylreductaseFAS, Fatty acid synthasesKR, KetoreductaseKS, KetosynthaseLM, Loading moduleLTTR, LysR-type transcriptional regulatorMetabolic engineeringNatural productsPCC, Propionyl-CoA carboxylasePDB, Precursor directed biosynthesisPK, PolyketidePKS, Polyketide synthasePolyketidePolyketide synthaseR, Reductase domainSARP, Streptomyces antibiotic regulatory proteinSNAC, N-acetylcysteamineSynthetic biologyTE, ThioesteraseTKL, Triketide lactone

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Area of Science:

  • Metabolic Engineering
  • Synthetic Biology
  • Biochemistry

Background:

  • Polyketides represent a vast and chemically diverse class of natural products.
  • Modular polyketide synthases (PKSs) offer a logical framework for generating this chemical diversity.
  • The utilization of non-native enzymatic machinery is crucial for producing novel compounds via metabolic engineering.

Purpose of the Study:

  • To review engineering efforts in modular polyketide synthases (PKSs).
  • To highlight the application of PKS engineering at both protein and cellular levels.
  • To examine future applications of engineered PKSs in producing valuable chemicals.

Main Methods:

  • Review of literature on PKS engineering strategies.
  • Analysis of protein-level engineering approaches for PKS modification.
  • Examination of cellular-level metabolic engineering strategies involving PKS.

Main Results:

  • Modular PKS engineering enables the production of a broad range of chemical functionalities.
  • Successful engineering at protein and cellular levels has been demonstrated for generating diverse structures.
  • PKS engineering provides access to both existing and novel polyketide compounds.

Conclusions:

  • Engineering modular polyketide synthases is a powerful strategy for metabolic engineering.
  • PKS engineering holds significant potential for the future production of medicines, fuels, and other industrial chemicals.
  • Further advancements in PKS engineering will expand the scope of bio-based chemical synthesis.