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Title: Synthesis of polyketides from low cost substrates by the thermotolerant yeast Kluyveromyces marxianus

Abstract

Abstract Kluyveromyces marxianus is a promising nonconventional yeast for biobased chemical production due to its rapid growth rate, high TCA cycle flux, and tolerance to low pH and high temperature. Unlike Saccharomyces cerevisiae, K. marxianus grows on low‐cost substrates to cell densities that equal or surpass densities in glucose, which can be beneficial for utilization of lignocellulosic biomass (xylose), biofuel production waste (glycerol), and whey (lactose). We have evaluated K. marxianus for the synthesis of polyketides, using triacetic acid lactone (TAL) as the product. The 2‐pyrone synthase (2‐PS) was expressed on a CEN/ARS plasmid in three different strains, and the effects of temperature, carbon source, and cultivation strategy on TAL levels were determined. The highest titer was obtained in defined 1% xylose medium at 37°C, with substantial titers at 41 and 43°C. The introduction of a high‐stability 2‐PS mutant and a promoter substitution increased titer four‐fold. 2‐PS expression from a multi‐copy pKD1‐based plasmid improved TAL titers a further five‐fold. Combining the best plasmid, promoter, and strain resulted in a TAL titer of 1.24 g/L and a yield of 0.0295 mol TAL/mol carbon for this otherwise unengineered strain in 3 ml tube culture. This is an excellent titer and yield (on xylose) before metabolic engineeringmore » or fed‐batch culture relative to other hosts (on glucose), and demonstrates the promise of this rapidly growing and thermotolerant yeast species for polyketide production.« less

Authors:
 [1];  [1];  [1]; ORCiD logo [1]
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  1. Univ. of California, Irvine, CA (United States)
Publication Date:
Research Org.:
Univ. of California, Riverside, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC); National Science Foundation (NSF)
OSTI Identifier:
1613105
Alternate Identifier(s):
OSTI ID: 1508686
Grant/Contract Number:  
SC0019093; CBET-1803677; EEC-0813570
Resource Type:
Accepted Manuscript
Journal Name:
Biotechnology and Bioengineering
Additional Journal Information:
Journal Volume: 116; Journal Issue: 7; Journal ID: ISSN 0006-3592
Publisher:
Wiley
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Biotechnology & applied microbiology; Kluyveromyces marxianus; polyketides thermotolerance; triacetic acid lactone; xylose

Citation Formats

McTaggart, Tami L., Bever, Danielle, Bassett, Shane, and Da Silva, Nancy A. Synthesis of polyketides from low cost substrates by the thermotolerant yeast Kluyveromyces marxianus. United States: N. p., 2019. Web. doi:10.1002/bit.26976.
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McTaggart, Tami L., Bever, Danielle, Bassett, Shane, & Da Silva, Nancy A. Synthesis of polyketides from low cost substrates by the thermotolerant yeast Kluyveromyces marxianus. United States. https://doi.org/10.1002/bit.26976
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McTaggart, Tami L., Bever, Danielle, Bassett, Shane, and Da Silva, Nancy A. Sun . "Synthesis of polyketides from low cost substrates by the thermotolerant yeast Kluyveromyces marxianus". United States. https://doi.org/10.1002/bit.26976. https://www.osti.gov/servlets/purl/1613105.
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@article{osti_1613105,
title = {Synthesis of polyketides from low cost substrates by the thermotolerant yeast Kluyveromyces marxianus},
author = {McTaggart, Tami L. and Bever, Danielle and Bassett, Shane and Da Silva, Nancy A.},
abstractNote = {Abstract Kluyveromyces marxianus is a promising nonconventional yeast for biobased chemical production due to its rapid growth rate, high TCA cycle flux, and tolerance to low pH and high temperature. Unlike Saccharomyces cerevisiae, K. marxianus grows on low‐cost substrates to cell densities that equal or surpass densities in glucose, which can be beneficial for utilization of lignocellulosic biomass (xylose), biofuel production waste (glycerol), and whey (lactose). We have evaluated K. marxianus for the synthesis of polyketides, using triacetic acid lactone (TAL) as the product. The 2‐pyrone synthase (2‐PS) was expressed on a CEN/ARS plasmid in three different strains, and the effects of temperature, carbon source, and cultivation strategy on TAL levels were determined. The highest titer was obtained in defined 1% xylose medium at 37°C, with substantial titers at 41 and 43°C. The introduction of a high‐stability 2‐PS mutant and a promoter substitution increased titer four‐fold. 2‐PS expression from a multi‐copy pKD1‐based plasmid improved TAL titers a further five‐fold. Combining the best plasmid, promoter, and strain resulted in a TAL titer of 1.24 g/L and a yield of 0.0295 mol TAL/mol carbon for this otherwise unengineered strain in 3 ml tube culture. This is an excellent titer and yield (on xylose) before metabolic engineering or fed‐batch culture relative to other hosts (on glucose), and demonstrates the promise of this rapidly growing and thermotolerant yeast species for polyketide production.},
doi = {10.1002/bit.26976},
journal = {Biotechnology and Bioengineering},
number = 7,
volume = 116,
place = {United States},
year = {Sun Mar 24 00:00:00 EDT 2019},
month = {Sun Mar 24 00:00:00 EDT 2019}
}
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