Microbial production of bi-functional molecules by diversification of the fatty acid pathway
Microbial production of bi-functional molecules by diversification of the fatty acid pathway
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DOI：
10.1016/j.ymben.2016.01.003
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发表时间：
2016-05-01
影响因子：
8.4
通讯作者：
Nikolau, Basil J.
中科院分区：
文献类型：
--
作者：
Garg, Shivani;Rizhsky, Ludmila;Nikolau, Basil J.
在其ω-末端化学官能化的脂肪酸在自然界中是罕见的，但提供独特的化学和物理性质，作为生物基聚合物、润滑剂和表面活性剂的原料具有广泛的工业应用。两个酶决定簇控制该ω-基团功能性，用于起始脂肪酸生物合成的适当酰基-CoA底物的可用性，以及可以在该过程的初始缩合反应中容纳该底物的脂肪酸合酶（FAS）变体。在II型FAS中，3-酮脂酰-ACP合酶III（KASIII）催化该初始缩合反应。我们表征了来自不同细菌来源的KASIIs，并鉴定了对非典型酰基辅酶A底物具有新底物特异性的变体，包括3-羟基丁酰辅酶A。使用Alicyclobacillus acidocaldarius KASIII，我们证明了FAS在两种生物工程微生物宿主中从葡萄糖中产生新型ω-1羟基支链脂肪酸的体内转移。这项研究揭示了KASIII用于合成多种omega-官能化脂肪酸的生物催化潜力。(C)2016国际代谢工程学会。爱思唯尔公司出版All rights reserved.
Fatty acids that are chemically functionalized at their omega-ends are rare in nature yet offer unique chemical and physical properties with wide ranging industrial applications as feedstocks for bio-based polymers, lubricants and surfactants. Two enzymatic determinants control this omega-group functionality, the availability of an appropriate acyl-CoA substrate for initiating fatty acid biosynthesis, and a fatty acid synthase (FAS) variant that can accommodate that substrate in the initial condensation reaction of the process. In Type II FAS, 3-ketoacyl-ACP synthase III (KASIII) catalyses this initial condensation reaction. We characterized KASIlls from diverse bacterial sources, and identified variants with novel substrate specificities towards atypical acyl-CoA substrates, including 3-hydroxybutyryl-CoA. Using Alicyclobacillus acidocaldarius KASIII, we demonstrate the in vivo diversion of FAS to produce novel omega-1 hydroxy-branched fatty acids from glucose in two bioengineered microbial hosts. This study unveils the biocatalytic potential of KASIII for synthesizing diverse omega-functionalized fatty acids. (C) 2016 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.