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Int. J. Mol. Sci. 2019, 20(3), 786;

Engineering of Fatty Acid Synthases (FASs) to Boost the Production of Medium-Chain Fatty Acids (MCFAs) in Mucor circinelloides

Colin Ratledge Center for Microbial Lipids, School of Agriculture Engineering and Food Science, Shandong University of Technology, Zibo 255049, China
Department of Biology, South Texas Center of Emerging Infectious Diseases (STCEID), University of Texas, San Antonio, TX 78249, USA
Departamento de Genética y Microbiología (Unidad asociada al IQFR-CSIC), Facultad de Biología, Universidad de Murcia, 30071 Murcia, Spain
These authors contributed equally to this work.
Author to whom correspondence should be addressed.
Received: 9 January 2019 / Revised: 6 February 2019 / Accepted: 9 February 2019 / Published: 12 February 2019
(This article belongs to the Section Molecular Microbiology)
Full-Text   |   PDF [2665 KB, uploaded 12 February 2019]   |  


Increasing energy demands and health-related concerns worldwide have motivated researchers to adopt diverse strategies to improve medium-chain fatty acid (MCFA) biosynthesis for use in the functional food and aviation industries. The abundance of naturally produced MCFAs from botanical sources (i.e., coconut fruit/seeds and palm tree) has been observed to be insufficient compared with the various microorganisms used to cope with industrial demands. Mucor circinelloides is one of many promising microorganisms; it exhibits diverse biotechnological importance ranging from the production of functional lipids to applications in the manufacture of bio-fuel. Thus, research was conducted to acquire the desired elevated amounts of MCFAs (i.e., C8–C12) from metabolically engineered strains of M. circinelloides M65. To achieve this goal, four different acyl-acyl carrier protein (ACP) thioesterase (TE)-encoding genes exhibiting a substrate preference for medium-chain acyl-ACP molecules were expressed in M. circinelloides M65, resulting in the generation of C8–C12 fatty acids. Among all the engineered strains, M65-TE-03 and M65-TE-04 demonstrated the highest production of non-native C8–C10 and C12 fatty acids, respectively, in comparison to the control. These recombinant strains biosynthesized MCFAs de novo within the range from 28 to 46% (i.e., 1.14 to 2.77 g/L) of total cell lipids. Moreover, the reduction in chain length eventually resulted in a 1.5–1.75-fold increase in total lipid productivity in the engineered strains. The MCFAs were also found to be integrated into all lipid classes. This work illustrates how the integration of heterologous enzymes in M. circinelloides can offer a novel opportunity to edit the fatty acid synthases (FAS) complex, resulting in increased production of microbial MFCAs. View Full-Text
Keywords: medium-chain fatty acids; metabolic engineering; Mucor circinelloides; microbial lipids; bio-fuels medium-chain fatty acids; metabolic engineering; Mucor circinelloides; microbial lipids; bio-fuels

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Hussain, S.A.; Hameed, A.; Khan, M.A.K.; Zhang, Y.; Zhang, H.; Garre, V.; Song, Y. Engineering of Fatty Acid Synthases (FASs) to Boost the Production of Medium-Chain Fatty Acids (MCFAs) in Mucor circinelloides. Int. J. Mol. Sci. 2019, 20, 786.

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