Metabolic engineering of Saccharomyces cerevisiae for de novo production of odd-numbered medium-chain fatty acids

IF 6.8 1区生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Metabolic engineering Pub Date : 2024-02-05 DOI:10.1016/j.ymben.2024.01.009

Genlai Dong , Ying Zhao , Wentao Ding , Shijie Xu , Qi Zhang , Huimin Zhao , Shuobo Shi

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引用次数: 0

Abstract

Odd-numbered fatty acids (FAs) have been widely used in nutrition, agriculture, and chemical industries. Recently, some studies showed that they could be produced from bacteria or yeast, but the products are almost exclusively odd-numbered long-chain FAs. Here we report the design and construction of two biosynthetic pathways in Saccharomyces cerevisiae for de novo production of odd-numbered medium-chain fatty acids (OMFAs) via ricinoleic acid and 10-hydroxystearic acid, respectively. The production of OMFAs was enabled by introducing a hydroxy fatty acid cleavage pathway, including an alcohol dehydrogenase from Micrococcus luteus, a Baeyer-Villiger monooxygenase from Pseudomonas putida, and a lipase from Pseudomonas fluorescens. These OMFA biosynthetic pathways were optimized by eliminating the rate-limiting step, generating heptanoic acid, 11-hydroxyundec-9-enoic acid, nonanoic acid, and 9-hydroxynonanoic acid at 7.83 mg/L, 9.68 mg/L, 9.43 mg/L and 13.48 mg/L, respectively. This work demonstrates the biological production of OMFAs in a sustainable manner in S. cerevisiae.

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从头生产奇数中链脂肪酸的酿酒酵母代谢工程

奇数脂肪酸（FA）已被广泛应用于营养、农业和化学工业。最近的一些研究表明，它们可以从细菌或酵母中产生，但产物几乎都是奇数长链脂肪酸。在此，我们报告了在酿酒酵母（Saccharomyces cerevisiae）中设计和构建了两条生物合成途径，分别通过蓖麻油酸和 10-羟基硬脂酸从头生产奇数中链脂肪酸（OMFAs）。通过引入羟基脂肪酸裂解途径（包括来自黄体微球菌的醇脱氢酶、来自假单胞菌的拜尔-维利格单氧酶和来自荧光假单胞菌的脂肪酶），实现了 OMFAs 的生产。通过取消限速步骤，优化了这些 OMFA 生物合成途径，生成的庚酸、11-羟基十一-9-烯酸、壬酸和 9-羟基壬酸的浓度分别为 7.83 毫克/升、9.68 毫克/升、9.43 毫克/升和 13.48 毫克/升。这项工作证明了 S. cerevisiae 能以可持续的方式生物生产 OMFAs。

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来源期刊

Metabolic engineering 工程技术-生物工程与应用微生物

CiteScore

15.60

自引率

6.00%

发文量

140

审稿时长

44 days

期刊介绍： Metabolic Engineering (MBE) is a journal that focuses on publishing original research papers on the directed modulation of metabolic pathways for metabolite overproduction or the enhancement of cellular properties. It welcomes papers that describe the engineering of native pathways and the synthesis of heterologous pathways to convert microorganisms into microbial cell factories. The journal covers experimental, computational, and modeling approaches for understanding metabolic pathways and manipulating them through genetic, media, or environmental means. Effective exploration of metabolic pathways necessitates the use of molecular biology and biochemistry methods, as well as engineering techniques for modeling and data analysis. MBE serves as a platform for interdisciplinary research in fields such as biochemistry, molecular biology, applied microbiology, cellular physiology, cellular nutrition in health and disease, and biochemical engineering. The journal publishes various types of papers, including original research papers and review papers. It is indexed and abstracted in databases such as Scopus, Embase, EMBiology, Current Contents - Life Sciences and Clinical Medicine, Science Citation Index, PubMed/Medline, CAS and Biotechnology Citation Index.