Microbial production of bi-functional molecules by diversification of the fatty acid pathway

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• 作者：Shivani Garg^a ; ^b ; ¹ ; ^{garg@iastate.edu" class="auth_mail" title="E-mail the corresponding author} ; Ludmila Rizhsky^a ; ^c ; ² ; ^{ludmilar@iastate.edu" class="auth_mail" title="E-mail the corresponding author} ; Huanan Jin^a ; ^b ; ^d ; ³ ; ^{huananjin@mail.hzau.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Xiaochen Yu^a ; ^b ; ^d ; ⁴ ; ^{yux@iastate.edu" class="auth_mail" title="E-mail the corresponding author} ; Fuyuan Jing^a ; ^b ; ⁵ ; ^{fyjing@iastate.edu" class="auth_mail" title="E-mail the corresponding author} ; Marna D. Yandeau-Nelson^b ; ^e ; ⁶ ; ^{myn@iastate.edu" class="auth_mail" title="E-mail the corresponding author} ; Basil J. Nikolau^a ; ^b ; ^d ; ⁷ ; ^{dimmas@iastate.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：KASIII ; 3-Ketoacyl-ACP-Synthase III ; HBFA ; ω-1 Hydroxy Branched Fatty Acid ; FAS ; Fatty Acid Synthase ; PHB ; Polyhydroxybutyrate
• 刊名：Metabolic Engineering
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：35
• 期：Complete
• 页码：9-20
• 全文大小：1482 K

文摘

Fatty acids that are chemically functionalized at their ω-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 ω-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 KASIIIs 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 ω-1 hydroxy-branched fatty acids from glucose in two bioengineered microbial hosts. This study unveils the biocatalytic potential of KASIII for synthesizing diverse ω-functionalized fatty acids.