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鉴定三酰基甘油重塑机制以合成含有不寻常脂肪酸的油脂。

Identification of triacylglycerol remodeling mechanism to synthesize unusual fatty acid containing oils.

机构信息

Institute of Biological Chemistry, Washington State University, Pullman, WA, 99164, USA.

United States Department of Agriculture, Agricultural Research Service, Western Regional Research Center, Albany, CA, 94710, USA.

出版信息

Nat Commun. 2024 Apr 26;15(1):3547. doi: 10.1038/s41467-024-47995-x.

Abstract

Typical plant membranes and storage lipids are comprised of five common fatty acids yet over 450 unusual fatty acids accumulate in seed oils of various plant species. Plant oils are important human and animal nutrients, while some unusual fatty acids such as hydroxylated fatty acids (HFA) are used in the chemical industry (lubricants, paints, polymers, cosmetics, etc.). Most unusual fatty acids are extracted from non-agronomic crops leading to high production costs. Attempts to engineer HFA into crops are unsuccessful due to bottlenecks in the overlapping pathways of oil and membrane lipid synthesis where HFA are not compatible. Physaria fendleri naturally overcomes these bottlenecks through a triacylglycerol (TAG) remodeling mechanism where HFA are incorporated into TAG after initial synthesis. TAG remodeling involves a unique TAG lipase and two diacylglycerol acyltransferases (DGAT) that are selective for different stereochemical and acyl-containing species of diacylglycerol within a synthesis, partial degradation, and resynthesis cycle. The TAG lipase interacts with DGAT1, localizes to the endoplasmic reticulum (with the DGATs) and to puncta around the lipid droplet, likely forming a TAG remodeling metabolon near the lipid droplet-ER junction. Each characterized DGAT and TAG lipase can increase HFA accumulation in engineered seed oils.

摘要

典型的植物膜和储存脂质由五种常见脂肪酸组成,但在各种植物种子油中积累了超过 450 种不常见的脂肪酸。植物油脂是人类和动物的重要营养物质,而一些不常见的脂肪酸,如羟基脂肪酸 (HFA),则用于化学工业(润滑剂、油漆、聚合物、化妆品等)。大多数不常见的脂肪酸是从非农业作物中提取的,导致生产成本很高。由于油和膜脂合成途径中的瓶颈,HFA 不兼容,因此将 HFA 工程化到作物中的尝试都没有成功。Physaria fendleri 通过三酰基甘油(TAG)重塑机制自然克服了这些瓶颈,其中 HFA 在初始合成后被掺入 TAG 中。TAG 重塑涉及一种独特的 TAG 脂肪酶和两种二酰基甘油酰基转移酶 (DGAT),它们在合成、部分降解和再合成循环中对不同立体化学和酰基含量的二酰基甘油具有选择性。TAG 脂肪酶与 DGAT1 相互作用,定位于内质网(与 DGATs 一起)和脂滴周围的斑点,可能在脂滴-ER 连接处附近形成一个 TAG 重塑代谢物。每个特征化的 DGAT 和 TAG 脂肪酶都可以增加工程化种子油中的 HFA 积累。

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