Programmable polyketide biosynthesis platform for production of aromatic compounds in yeast

Tadas Jakočiūnas; Andreas K Klitgaard; Eftychia Eva Kontou; Julie Bang Nielsen; Emil Thomsen; David Romero-Suarez; Kai Blin; Christopher J Petzold; Jennifer W Gin; Yaojun Tong; Charlotte Held Gotfredsen; Pep Charusanti; Rasmus J N Frandsen; Tilmann Weber; Sang Yup Lee; Michael K Jensen; Jay D Keasling

doi:10.1016/j.synbio.2020.01.004

Programmable polyketide biosynthesis platform for production of aromatic compounds in yeast

Synth Syst Biotechnol. 2020 Jan 23;5(1):11-18. doi: 10.1016/j.synbio.2020.01.004. eCollection 2020 Mar.

Authors

Tadas Jakočiūnas¹, Andreas K Klitgaard¹, Eftychia Eva Kontou¹, Julie Bang Nielsen¹, Emil Thomsen¹, David Romero-Suarez¹, Kai Blin¹, Christopher J Petzold², Jennifer W Gin², Yaojun Tong¹, Charlotte Held Gotfredsen³, Pep Charusanti¹, Rasmus J N Frandsen⁴, Tilmann Weber¹, Sang Yup Lee^{1

5}, Michael K Jensen¹, Jay D Keasling^{1

2

6

7

8}

Affiliations

¹ The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kgs. Lyngby, Denmark.
² Joint BioEnergy Institute, Emeryville, CA, USA.
³ Department of Chemistry, Technical University of Denmark, Kgs. Lyngby, Denmark.
⁴ Department of Biotechnology and Biomedicine, Technical University of Denmark, Kgs. Lyngby, Denmark.
⁵ Department of Chemical and Biomolecular Engineering (BK21 Plus Program), Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea.
⁶ Biological Systems & Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
⁷ Department of Chemical and Biomolecular Engineering & Department of Bioengineering University of California, Berkeley, CA, USA.
⁸ Center for Synthetic Biochemistry, Institute for Synthetic Biology, Shenzhen Institutes for Advanced Technologies, Shenzhen, China.

Abstract

To accelerate the shift to bio-based production and overcome complicated functional implementation of natural and artificial biosynthetic pathways to industry relevant organisms, development of new, versatile, bio-based production platforms is required. Here we present a novel yeast-based platform for biosynthesis of bacterial aromatic polyketides. The platform is based on a synthetic polyketide synthase system enabling a first demonstration of bacterial aromatic polyketide biosynthesis in a eukaryotic host.

Keywords: Aromatic polyketides; Biotechnology; CRISPR/Cas9; Metabolic engineering; Natural products; Polyketide; Production platform in eukaryotes; Synthetic biology.