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Accelerating polyketide synthase engineering for high TRY production of biofuels and bioproducts (Final Technical Report)

Technical Report ·
DOI:https://doi.org/10.2172/2279068· OSTI ID:2279068
 [1];  [2];  [2];  [2];  [2];  [3];  [4];  [5]
  1. Univ. of California, Berkeley, CA (United States); University of California Berkeley
  2. Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
  3. Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
  4. National Renewable Energy Laboratory (NREL), Golden, CO (United States)
  5. Argonne National Laboratory (ANL), Argonne, IL (United States)
+ Show Author Affiliations

Polyketide synthase (PKS) enzymes have a modular, deterministic logic that holds the potential to act as a flexible chemical factory for the biological production of a huge diversity of valuable small molecule compounds. However, engineering a custom PKS to produce a specific desired product currently requires years of trial and error, for reasons that remain poorly understood. In this project, we have developed a rapid, high throughput, Design-Build-Test-Learn (DBTL) cycle for polyketide synthases (PKSs) and demonstrate its utility for production of materials precursors. The objectives are 1) to develop a rapid, high-throughput (HT) DBTL cycle for PKSs that will enable production of a large number of unnatural, organic molecules on demand at high titer, rate, and yield (TRY); 2) to demonstrate the utility of the PKS DBTL cycle to produce three molecules: one commodity chemical (caprolactam or valerolactam) and two novel materials precursors (caprolactam or valerolactam derivatives); and 3) to demonstrate the utility of the PKS DBTL cycle to increase the TRY of one molecule (caprolactam or valerolactam). In this project, we have successfully demonstrated our high throughput PKS DBTL pipeline, and have biologically produced valerolactam and several other novel nylon monomers.

Research Organization:
Univ. of California, Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Energy Efficiency and Renewable Energy (EERE), Office of Sustainable Transportation. Bioenergy Technologies Office (BETO)
DOE Contract Number:
EE0008926
OSTI ID:
2279068
Report Number(s):
DOE-UCB--08926-1
Country of Publication:
United States
Language:
English

References (1)

ClusterCAD 2.0: an updated computational platform for chimeric type I polyketide synthase and nonribosomal peptide synthetase design journal November 2022

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Related Subjects

60 APPLIED LIFE SCIENCES
Polyketide synthase
laboratory automation
machine learning