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脂肪酸合酶(FASs)的工程改造以提高. 中链脂肪酸(MCFAs)的产量。

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

机构信息

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.

出版信息

Int J Mol Sci. 2019 Feb 12;20(3):786. doi: 10.3390/ijms20030786.

DOI:10.3390/ijms20030786
PMID:30759801
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6387429/
Abstract

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. 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 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 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 can offer a novel opportunity to edit the fatty acid synthases (FAS) complex, resulting in increased production of microbial MFCAs.

摘要

全球不断增长的能源需求和与健康相关的问题促使研究人员采用各种策略来提高中链脂肪酸(MCFA)的生物合成,以用于功能性食品和航空工业。与各种用于应对工业需求的微生物相比,从植物来源(即椰子果实/种子和棕榈树)中天然产生的 MCFA 的丰度被认为是不足的。 是许多有前途的微生物之一;它具有多种生物技术重要性,从功能性脂质的生产到生物燃料制造中的应用。因此,进行了研究以从代谢工程菌株 M65 中获得所需的大量 MCFA(即 C8⁻C12)。为了实现这一目标,在 M65 中表达了四种不同的酰基辅酶 A(ACP)硫酯酶(TE)编码基因,它们对中链酰-ACP 分子表现出底物偏好,从而产生 C8⁻C12 脂肪酸。在所有工程菌株中,与对照相比,M65-TE-03 和 M65-TE-04 分别表现出最高的非天然 C8⁻C10 和 C12 脂肪酸的生产。这些重组菌株在总细胞脂质的 28%至 46%(即 1.14 至 2.77 g/L)范围内从头生物合成 MCFA。此外,链长的缩短最终导致工程菌株的总脂生产力提高了 1.5 至 1.75 倍。还发现 MCFA 整合到所有脂质类别中。这项工作说明了如何在 中整合异源酶可以为编辑脂肪酸合酶(FAS)复合物提供新的机会,从而增加微生物 MCFA 的产量。

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