酵母中的组合生物合成可产生 200 多种二萜类化合物

IF 6.8 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Maximilian Frey , Ulschan Bathe , Luca Meink , Gerd U. Balcke , Jürgen Schmidt , Andrej Frolov , Alena Soboleva , Ahmed Hassanin , Mehdi D. Davari , Oliver Frank , Verena Schlagbauer , Corinna Dawid , Alain Tissier
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引用次数: 0

摘要

二萜类化合物是一类多种多样的天然产物,其中许多已经或可能成为药物或工业化学品。二萜生物合成的模块化特征和相关酶的杂交性使组合生物合成成为生成多种二萜化合物库的一种有前途的方法。在这里,我们报告了在酵母中以不同的组合方式组装 10 种产生 (+)-copalyl diphosphate-derived 骨架的二萜合成酶和 4 种细胞色素 P450 加氧酶(CYPs)的情况。由此产生了 200 多种二萜类化合物。根据文献和化学数据库搜索,这些化合物中有 162 种可被视为自然界的新化合物。这些 CYPs 接受了大部分底物,但仍具有区域选择性,只有少数例外。我们的研究结果为利用序列数据库系统探索酵母中的二萜化学空间奠定了基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Combinatorial biosynthesis in yeast leads to over 200 diterpenoids

Combinatorial biosynthesis in yeast leads to over 200 diterpenoids

Diterpenoids form a diverse group of natural products, many of which are or could become pharmaceuticals or industrial chemicals. The modular character of diterpene biosynthesis and the promiscuity of the enzymes involved make combinatorial biosynthesis a promising approach to generate libraries of diverse diterpenoids. Here, we report on the combinatorial assembly in yeast of ten diterpene synthases producing (+)-copalyl diphosphate-derived backbones and four cytochrome P450 oxygenases (CYPs) in diverse combinations. This resulted in the production of over 200 diterpenoids. Based on literature and chemical database searches, 162 of these compounds can be considered new-to-Nature. The CYPs accepted most substrates they were given but remained regioselective with few exceptions. Our results provide the basis for the systematic exploration of the diterpenoid chemical space in yeast using sequence databases.

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来源期刊
Metabolic engineering
Metabolic engineering 工程技术-生物工程与应用微生物
CiteScore
15.60
自引率
6.00%
发文量
140
审稿时长
44 days
期刊介绍: Metabolic Engineering (MBE) is a journal that focuses on publishing original research papers on the directed modulation of metabolic pathways for metabolite overproduction or the enhancement of cellular properties. It welcomes papers that describe the engineering of native pathways and the synthesis of heterologous pathways to convert microorganisms into microbial cell factories. The journal covers experimental, computational, and modeling approaches for understanding metabolic pathways and manipulating them through genetic, media, or environmental means. Effective exploration of metabolic pathways necessitates the use of molecular biology and biochemistry methods, as well as engineering techniques for modeling and data analysis. MBE serves as a platform for interdisciplinary research in fields such as biochemistry, molecular biology, applied microbiology, cellular physiology, cellular nutrition in health and disease, and biochemical engineering. The journal publishes various types of papers, including original research papers and review papers. It is indexed and abstracted in databases such as Scopus, Embase, EMBiology, Current Contents - Life Sciences and Clinical Medicine, Science Citation Index, PubMed/Medline, CAS and Biotechnology Citation Index.
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