Engineering of Fatty Acid Synthases (FASs) to Boost the Production of Medium-Chain Fatty Acids (MCFAs) in Mucor circinelloides
Engineering of Fatty Acid Synthases (FASs) to Boost the Production of Medium-Chain Fatty Acids (MCFAs) in Mucor circinelloides
复制标题
脂肪酸合成酶 (FAS) 工程可提高卷枝毛霉中中链脂肪酸 (MCFA) 的产量
DOI：
10.3390/ijms20030786
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发表时间：
2019-02-01
影响因子：
5.6
通讯作者：
Song, Yuanda
中科院分区：
文献类型：
--
作者：
Hussain, Syed Ammar;Hameed, Ahsan;Song, Yuanda
全球范围内不断增长的能源需求以及与健康相关的问题促使研究人员采取多种策略来改进中链脂肪酸（MCFA）的生物合成，以用于功能性食品和航空工业。与用于满足工业需求的各种微生物相比，已观察到植物来源（即椰子果实/种子和棕榈树）天然产生的中链脂肪酸数量不足。卷枝毛霉是众多有前景的微生物之一；它在生物技术方面具有多种重要性，从生产功能性脂质到应用于生物燃料制造。因此，进行了研究以从卷枝毛霉M65的代谢工程菌株中获取所需的更高含量的中链脂肪酸（即C8 - C12）。为实现这一目标，在卷枝毛霉M65中表达了四个对中链酰基 - 酰基载体蛋白（ACP）分子具有底物偏好的不同酰基 - 酰基载体蛋白硫酯酶（TE）编码基因，从而产生了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分别显示出最高的非天然C8 - C10和C12脂肪酸产量。这些重组菌株从头生物合成的中链脂肪酸占细胞总脂质的28% - 46%（即1.14 - 2.77克/升）。此外，链长的减少最终导致工程菌株的总脂质生产率提高了1.5 - 1.75倍。还发现中链脂肪酸被整合到所有脂质类别中。这项工作说明了在卷枝毛霉中整合异源酶如何为编辑脂肪酸合酶（FAS）复合物提供新的机会，从而提高微生物中链脂肪酸的产量。
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.