Biosciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee, USA.
Process Chemistry, Codexis, Inc., Redwood City, California, USA.
Nat Prod Rep. 2020 Aug 19;37(8):1122-1143. doi: 10.1039/c9np00071b.
Covering: 2000 to 2020 Natural products and their derivatives are commercially important medicines, agrochemicals, flavors, fragrances, and food ingredients. Industrial strategies to produce these structurally complex molecules encompass varied combinations of chemical synthesis, biocatalysis, and extraction from natural sources. Interest in engineering natural product biosynthesis began with the advent of genetic tools for pathway discovery. Genes and strains can now readily be synthesized, mutated, recombined, and sequenced. Enzyme engineering has succeeded commercially due to the development of genetic methods, analytical technologies, and machine learning algorithms. Today, engineered biosynthetic enzymes from organisms spanning the tree of life are used industrially to produce diverse molecules. These biocatalytic processes include single enzymatic steps, multienzyme cascades, and engineered native and heterologous microbial strains. This review will describe how biosynthetic enzymes have been engineered to enable commercial and near-commercial syntheses of natural products and their analogs.
2000 年至 2020 年 天然产物及其衍生物是具有商业重要性的药物、农用化学品、香料、香精和食品成分。生产这些结构复杂分子的工业策略包括化学合成、生物催化和从天然来源提取的各种组合。随着用于途径发现的遗传工具的出现，人们对工程天然产物生物合成产生了兴趣。现在可以轻松地合成、突变、重组和测序基因和菌株。由于遗传方法、分析技术和机器学习算法的发展，酶工程在商业上取得了成功。如今，来自生命之树各个分支的工程化生物合成酶被用于工业生产各种分子。这些生物催化过程包括单酶步骤、多酶级联和工程化的天然和异源微生物菌株。本文将介绍如何对生物合成酶进行工程改造，以实现天然产物及其类似物的商业和接近商业合成。
