TY - JOUR
T1 - Exploring engineering strategies that enhance de novo production of exotic cyclopropane fatty acids in Saccharomyces cerevisiae
AU - Jiang, Wei
AU - Peng, Huadong
AU - He, Lizhong
AU - Lesma-Amaro, Rodrigo
AU - Haritos, Victoria S.
N1 - Funding Information:
W.J. was financially supported by Monash University for Monash Graduate Scholarship (MGS) and Monash International Tuition Scholarships (MITS), and Graduate Research International Travel Award (GRITA). R.L.A. and H.P. received funding from BBSRC (BB/R01602X/1). We would like to extend our appreciation to Dr. Lavaraj Devkota for his valuable assistance in performing the gas chromatography analysis. Open access publishing facilitated by Monash University, as part of the Wiley - Monash University agreement via the Council of Australian University Librarians.
Funding Information:
W.J. was financially supported by Monash University for Monash Graduate Scholarship (MGS) and Monash International Tuition Scholarships (MITS), and Graduate Research International Travel Award (GRITA). R.L.A. and H.P. received funding from BBSRC (BB/R01602X/1). We would like to extend our appreciation to Dr. Lavaraj Devkota for his valuable assistance in performing the gas chromatography analysis.
Publisher Copyright:
© 2024 The Authors. Biotechnology Journal published by Wiley-VCH GmbH.
PY - 2024/2
Y1 - 2024/2
N2 - Cycloalkanes have broad applications as specialty fuels, lubricants, and pharmaceuticals but are not currently available from renewable sources, whereas, production of microbial cycloalkanes such as cyclopropane fatty acids (CFA) has bottlenecks. Here, a systematic investigation was undertaken into the biosynthesis of CFA in Saccharomyces cerevisiae heterologously expressing bacterial CFA synthase. The enzyme catalyzes formation of a 3-membered ring in unsaturated fatty acids. Monounsaturated fatty acids in phospholipids (PL) are the site of CFA synthesis; precursor cis-Δ9 C16 and C18 fatty acids were enhanced through OLE1 and SAM2 overexpression which enhanced CFA in PL. CFA turnover from PL to storage in triacylglycerols (TAG) was achieved by phospholipase PBL2 overexpression and acyl-CoA synthase to increase flux to TAG. Consequently, CFA storage as TAG reached 12 mg g−1 DCW, improved 3-fold over the base strain and >22% of TAG was CFA. Our research improves understanding of cycloalkane biosynthesis in yeast and offers insights into processing of other exotic fatty acids.
AB - Cycloalkanes have broad applications as specialty fuels, lubricants, and pharmaceuticals but are not currently available from renewable sources, whereas, production of microbial cycloalkanes such as cyclopropane fatty acids (CFA) has bottlenecks. Here, a systematic investigation was undertaken into the biosynthesis of CFA in Saccharomyces cerevisiae heterologously expressing bacterial CFA synthase. The enzyme catalyzes formation of a 3-membered ring in unsaturated fatty acids. Monounsaturated fatty acids in phospholipids (PL) are the site of CFA synthesis; precursor cis-Δ9 C16 and C18 fatty acids were enhanced through OLE1 and SAM2 overexpression which enhanced CFA in PL. CFA turnover from PL to storage in triacylglycerols (TAG) was achieved by phospholipase PBL2 overexpression and acyl-CoA synthase to increase flux to TAG. Consequently, CFA storage as TAG reached 12 mg g−1 DCW, improved 3-fold over the base strain and >22% of TAG was CFA. Our research improves understanding of cycloalkane biosynthesis in yeast and offers insights into processing of other exotic fatty acids.
KW - exotic fatty acid
KW - lipid metabolism
KW - metabolic engineering
KW - synthetic biology
KW - triacylglycerol
UR - http://www.scopus.com/inward/record.url?scp=85185884862&partnerID=8YFLogxK
U2 - 10.1002/biot.202300694
DO - 10.1002/biot.202300694
M3 - Article
C2 - 38403410
AN - SCOPUS:85185884862
SN - 1860-6768
VL - 19
JO - Biotechnology Journal
JF - Biotechnology Journal
IS - 2
M1 - 2300694
ER -
