Averesch Nils J H, Krömer Jens O
Universities Space Research Association at NASA Ames Research Center, Moffett Field, CA, United States.
Department of Solar Materials, Helmholtz Centre for Environmental Research, Leipzig, Germany.
Front Bioeng Biotechnol. 2018 Mar 26;6:32. doi: 10.3389/fbioe.2018.00032. eCollection 2018.
The aromatic nature of shikimate pathway intermediates gives rise to a wealth of potential bio-replacements for commonly fossil fuel-derived aromatics, as well as naturally produced secondary metabolites. Through metabolic engineering, the abundance of certain intermediates may be increased, while draining flux from other branches off the pathway. Often targets for genetic engineering lie beyond the shikimate pathway, altering flux deep in central metabolism. This has been extensively used to develop microbial production systems for a variety of compounds valuable in chemical industry, including aromatic and non-aromatic acids like muconic acid, -hydroxybenzoic acid, and -coumaric acid, as well as aminobenzoic acids and aromatic α-amino acids. Further, many natural products and secondary metabolites that are valuable in food- and pharma-industry are formed outgoing from shikimate pathway intermediates. (Re)construction of such routes has been shown by production of resveratrol, reticuline, opioids, and vanillin. In this review, strain construction strategies are compared across organisms and put into perspective with requirements by industry for commercial viability. Focus is put on enhancing flux to and through shikimate pathway, and engineering strategies are assessed in order to provide a guideline for future optimizations.
莽草酸途径中间体的芳香性为常见的化石燃料衍生芳烃以及天然产生的次生代谢产物带来了大量潜在的生物替代物。通过代谢工程，可以增加某些中间体的丰度，同时减少途径中其他分支的通量。基因工程的目标通常位于莽草酸途径之外，改变中心代谢的深层通量。这已被广泛用于开发微生物生产系统，以生产化学工业中各种有价值的化合物，包括芳香族和非芳香族酸，如粘康酸、对羟基苯甲酸和对香豆酸，以及氨基苯甲酸和芳香族α-氨基酸。此外，许多在食品和制药工业中有价值的天然产物和次生代谢产物都是由莽草酸途径中间体衍生而来的。白藜芦醇、网叶番荔枝碱、阿片类药物和香草醛的生产表明了此类途径的（重新）构建。在本综述中，比较了不同生物体的菌株构建策略，并结合行业对商业可行性的要求进行了展望。重点是增强通向莽草酸途径并通过该途径的通量，并评估工程策略，以便为未来的优化提供指导。
