Synthetic and systems biology for microbial production of commodity chemicals.
Synthetic and systems biology for microbial production of commodity chemicals.
复制标题
DOI：
10.1038/npjsba.2016.9
复制
发表时间：
2016
影响因子：
4
通讯作者：
Martín HG
中科院分区：
文献类型：
--
作者：
Chubukov V;Mukhopadhyay A;Petzold CJ;Keasling JD;Martín HG
合成生物学和系统生物学的结合是研究生物学基本问题和生产可立即实际应用的化学品（例如生物燃料、聚合物或治疗药物）的强大框架。然而，我们还无法像设计物理系统那样轻松而精确地设计生物系统。在这篇综述中，我们描述了从选择目标分子到将生产规模扩大到商业规模的路径。我们提出并解释了当前我们必须克服的一些挑战和知识差距，以便使我们的生物工程能力达到其他工程学科的水平。挑战始于分子选择，必须在经济潜力和生物可行性之间取得艰难的平衡。最近，新一代测序和 DNA 合成能力的指数级提高彻底改变了通路的设计和构建。尽管通过蛋白质组学的酶表达表征可以显着帮助途径优化，但选择最佳相对蛋白质表达水平以获得最大产量仍然是启发式、非系统方法的主题。有毒的代谢中间体和蛋白质可以显着影响生产，而动态途径调节成为预防这种情况的强大但尚不成熟的工具。宿主工程的出现是对途径工程的补充，以实现高生物产品产量；需要系统生物学方法，例如化学计量建模或生长耦合策略。最后一个常常被低估的挑战是成功地将工艺规模扩大到商业规模。生物工程的进一步发展需要持续努力提高可重复性和可预测性。
The combination of synthetic and systems biology is a powerful framework to study fundamental questions in biology and produce chemicals of immediate practical application such as biofuels, polymers, or therapeutics. However, we cannot yet engineer biological systems as easily and precisely as we engineer physical systems. In this review, we describe the path from the choice of target molecule to scaling production up to commercial volumes. We present and explain some of the current challenges and gaps in our knowledge that must be overcome in order to bring our bioengineering capabilities to the level of other engineering disciplines. Challenges start at molecule selection, where a difficult balance between economic potential and biological feasibility must be struck. Pathway design and construction have recently been revolutionized by next-generation sequencing and exponentially improving DNA synthesis capabilities. Although pathway optimization can be significantly aided by enzyme expression characterization through proteomics, choosing optimal relative protein expression levels for maximum production is still the subject of heuristic, non-systematic approaches. Toxic metabolic intermediates and proteins can significantly affect production, and dynamic pathway regulation emerges as a powerful but yet immature tool to prevent it. Host engineering arises as a much needed complement to pathway engineering for high bioproduct yields; and systems biology approaches such as stoichiometric modeling or growth coupling strategies are required. A final, and often underestimated, challenge is the successful scale up of processes to commercial volumes. Sustained efforts in improving reproducibility and predictability are needed for further development of bioengineering.
登录
查看更多内容
DOI：
10.1126/science.1191652
发表时间：
2010-10-01
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Ajikumar PK;Xiao WH;Tyo KE;Wang Y;Simeon F;Leonard E;Mucha O;Phon TH;Pfeifer B;Stephanopoulos G
通讯作者：
Stephanopoulos G
影响因子：
6.3
作者：
Chen L;Wu L;Wang J;Zhang W
通讯作者：
Zhang W
影响因子：
9.9
作者：
Brynildsen, Mark P.;Liao, James C.
通讯作者：
Liao, James C.
影响因子：
14.9
作者：
Carbonell P;Parutto P;Herisson J;Pandit SB;Faulon JL
通讯作者：
Faulon JL
影响因子：
3.3
作者：
Arike, L.;Valgepea, K.;Vilu, R.
通讯作者：
Vilu, R.