A biosynthetic pathway for hexanoic acid production in Kluyveromyces marxianus

Yuna Cheon, Jun Seob Kim, Jun Bum Park, Paul Heo, Jae Hyung Lim, Gyoo Yeol Jung, Jin Ho Seo, Jin Hwan Park, Hyun Min Koo, Kwang Myung Cho, Jin Byung Park, Suk Jin Ha, Dae Hyuk Kweon

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Hexanoic acid can be used for diverse industrial applications and is a precursor for fine chemistry. Although some natural microorganisms have been screened and evolved to produce hexanoic acid, the construction of an engineered biosynthetic pathway for producing hexanoic acid in yeast has not been reported. Here we constructed hexanoic acid pathways in Kluyveromyces marxianus by integrating 5 combinations of seven genes (AtoB, BktB, Crt, Hbd, MCT1, Ter, and TES1), by which random chromosomal sites of the strain are overwritten by the new genes from bacteria and yeast. One recombinant strain, H4A, which contained AtoB, BktB, Crt, Hbd, and Ter, produced 154. mg/L of hexanoic acid from galactose as the sole substrate. However, the hexanoic acid produced by the H4A strain was re-assimilated during the fermentation due to the reverse activity of AtoB, which condenses two acetyl-CoAs into a single acetoacetyl-CoA. This product instability could be overcome by the replacement of AtoB with a malonyl CoA-acyl carrier protein transacylase (MCT1) from Saccharomyces cerevisiae. Our results suggest that Mct1 provides a slow but stable acetyl-CoA chain elongation pathway, whereas the AtoB-mediated route is fast but unstable. In conclusion, hexanoic acid was produced for the first time in yeast by the construction of chain elongation pathways comprising 5-7 genes in K. marxianus.

Original languageEnglish
Pages (from-to)30-36
Number of pages7
JournalJournal of Biotechnology
Issue number1
StatePublished - 20 Jul 2014

Bibliographical note

Funding Information:
This research was supported by a grant from the Marine Biotechnology Program funded by the Ministry of Land, Transport, and Maritime Affairs of Korea, by Institute of Planning and Evaluation for Technology of Ministry for Food, Agriculture, Forestry and Fisheries, and by the Basic Science Research Program through the National Research Foundation of Korea grant funded by the Ministry of Science, ICT, & Future Planning ( 2009-0083540 ).


  • AtoB
  • Hexanoic acid
  • Kluyveromyces marxianus
  • MCT1
  • TES1


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