工程化微生物宿主用于生产细菌天然产物。
Engineering microbial hosts for production of bacterial natural products.
作者信息
Zhang Mingzi M, Wang Yajie, Ang Ee Lui, Zhao Huimin
机构信息
Metabolic Engineering Research Laboratory, Science and Engineering Institutes, Agency for Science, Technology and Research, Singapore.
出版信息
Nat Prod Rep. 2016 Aug 27;33(8):963-87. doi: 10.1039/c6np00017g. Epub 2016 Apr 13.
Abstract
Covering up to end 2015Microbial fermentation provides an attractive alternative to chemical synthesis for the production of structurally complex natural products. In most cases, however, production titers are low and need to be improved for compound characterization and/or commercial production. Owing to advances in functional genomics and genetic engineering technologies, microbial hosts can be engineered to overproduce a desired natural product, greatly accelerating the traditionally time-consuming strain improvement process. This review covers recent developments and challenges in the engineering of native and heterologous microbial hosts for the production of bacterial natural products, focusing on the genetic tools and strategies for strain improvement. Special emphasis is placed on bioactive secondary metabolites from actinomycetes. The considerations for the choice of host systems will also be discussed in this review.
摘要
涵盖至2015年底
微生物发酵为结构复杂的天然产物生产提供了一种有吸引力的化学合成替代方法。然而，在大多数情况下，生产滴度较低，需要提高以用于化合物表征和/或商业生产。由于功能基因组学和基因工程技术的进步，可以对微生物宿主进行工程改造以过量生产所需的天然产物，极大地加速了传统上耗时的菌株改良过程。本综述涵盖了用于生产细菌天然产物的天然和异源微生物宿主工程的最新进展和挑战，重点是菌株改良的遗传工具和策略。特别强调了放线菌产生的生物活性次级代谢产物。本综述还将讨论宿主系统选择的考虑因素。
相似文献
1
Engineering microbial hosts for production of bacterial natural products.工程化微生物宿主用于生产细菌天然产物。
Nat Prod Rep. 2016 Aug 27;33(8):963-87. doi: 10.1039/c6np00017g. Epub 2016 Apr 13.
2
Heterologous expression of bacterial natural product biosynthetic pathways.细菌天然产物生物合成途径的异源表达。
Nat Prod Rep. 2019 Oct 16;36(10):1412-1436. doi: 10.1039/c8np00091c.
3
Promoter engineering of natural product biosynthetic gene clusters in actinomycetes: concepts and applications.放线菌中天然产物生物合成基因簇的启动子工程：概念与应用。
Nat Prod Rep. 2024 Apr 24;41(4):672-699. doi: 10.1039/d3np00049d.
4
as a host for natural product discovery and engineering of biosynthetic gene clusters.作为天然产物发现和生物合成基因簇工程的宿主。
Nat Prod Rep. 2024 Jul 17;41(7):1113-1151. doi: 10.1039/d3np00065f.
5
Prospecting for new bacterial metabolites: a glossary of approaches for inducing, activating and upregulating the biosynthesis of bacterial cryptic or silent natural products.探寻新的细菌代谢产物：诱导、激活和上调细菌隐匿或沉默天然产物生物合成的方法概述。
Nat Prod Rep. 2016 Jan;33(1):54-72. doi: 10.1039/c5np00111k.
6
[Synthetic biology toward microbial secondary metabolites and pharmaceuticals].[面向微生物次级代谢产物和药物的合成生物学]
Yao Xue Xue Bao. 2013 Feb;48(2):155-60.
7
Rational engineering strategies for achieving high-yield, high-quality and high-stability of natural product production in actinomycetes.理性工程策略在放线菌中实现天然产物生产的高产量、高质量和高稳定性。
Metab Eng. 2021 Sep;67:198-215. doi: 10.1016/j.ymben.2021.06.003. Epub 2021 Jun 22.
8
Marine Proteobacteria as a source of natural products: advances in molecular tools and strategies.海洋变形菌门作为天然产物的来源：分子工具和策略的进展。
Nat Prod Rep. 2019 Sep 1;36(9):1333-1350. doi: 10.1039/c9np00020h. Epub 2019 Sep 6.
9
Synthetic biology and metabolic engineering of actinomycetes for natural product discovery.放线菌天然产物发现的合成生物学与代谢工程
Biotechnol Adv. 2019 Nov 1;37(6):107366. doi: 10.1016/j.biotechadv.2019.03.005. Epub 2019 Mar 7.
10
Challenges and advances in genetic manipulation of filamentous actinomycetes - the remarkable producers of specialized metabolites.丝状放线菌遗传操作的挑战与进展——特殊代谢产物的杰出生产者。
Nat Prod Rep. 2019 Sep 1;36(9):1351-1369. doi: 10.1039/c9np00029a. Epub 2019 Sep 13.
引用本文的文献
1
Scale-down bioreactors-comparative analysis of configurations.小型生物反应器——配置的比较分析
Bioprocess Biosyst Eng. 2025 Jun 5. doi: 10.1007/s00449-025-03182-w.
2
Strategies for Actinobacteria Isolation, Cultivation, and Metabolite Production that Are Biologically Important.放线菌分离、培养及代谢产物生产的生物学重要策略。
ACS Omega. 2025 Apr 18;10(16):15923-15934. doi: 10.1021/acsomega.5c01344. eCollection 2025 Apr 29.
3
Insights into Heterocycle Biosynthesis in the Cytotoxic Polyketide Alkaloid Janustatin A from a Plant-Associated Bacterium.对来自一种植物相关细菌的细胞毒性聚酮类生物碱贾努他汀A中杂环生物合成的见解。
Biochemistry. 2025 Jan 21;64(2):357-363. doi: 10.1021/acs.biochem.4c00542. Epub 2025 Jan 9.
4
CRISPR-Cas9-based genome-editing technologies in engineering bacteria for the production of plant-derived terpenoids.基于CRISPR-Cas9的基因组编辑技术在工程菌中用于生产植物源萜类化合物。
Eng Microbiol. 2024 May 28;4(3):100154. doi: 10.1016/j.engmic.2024.100154. eCollection 2024 Sep.
5
Harnessing bacterial metabolites for enhanced cancer chemotherapy: unveiling unique therapeutic potentials.利用细菌代谢物增强癌症化疗：揭示独特的治疗潜力。
Arch Microbiol. 2024 Oct 29;206(11):449. doi: 10.1007/s00203-024-04179-x.
6
Discovery, characterization, and engineering of an advantageous Streptomyces host for heterologous expression of natural product biosynthetic gene clusters.发现、鉴定和工程化具有优势的链霉菌宿主用于天然产物生物合成基因簇的异源表达。
Microb Cell Fact. 2024 May 24;23(1):149. doi: 10.1186/s12934-024-02416-y.
7
Combinatorial metabolic engineering of Streptomyces sp. CB03234-S for the enhanced production of anthraquinone-fused enediyne tiancimycins.组合代谢工程化链霉菌 CB03234-S 以提高蒽醌融合烯二炔天蚕霉素的产量。
Microb Cell Fact. 2024 May 4;23(1):128. doi: 10.1186/s12934-024-02399-w.
8
Oxytetracycline hyper-production through targeted genome reduction of .通过靶向基因组减少. 实现土霉素的高产。
mSystems. 2024 May 16;9(5):e0025024. doi: 10.1128/msystems.00250-24. Epub 2024 Apr 2.
9
The flavohaemoprotein hmp maintains redox homeostasis in response to reactive oxygen and nitrogen species in Corynebacterium glutamicum.黄素血红蛋白 hmp 可维持氧化还原平衡，以应对谷氨酸棒杆菌中的活性氧和活性氮物质。
Microb Cell Fact. 2023 Aug 18;22(1):158. doi: 10.1186/s12934-023-02160-9.
10
Understanding Autologous Spliceostatin Transcriptional Regulation to Derive Parts for Heterologous Expression in a Bacterial Host.理解自体剪接抑制转录调控，以在细菌宿主中获得异源表达的部分。
ACS Synth Biol. 2023 Jul 21;12(7):1952-1960. doi: 10.1021/acssynbio.3c00228. Epub 2023 Jun 20.
本文引用的文献
1
Inhibitory effects of epigallocatechin gallate and its glucoside on the human intestinal maltase inhibition.表没食子儿茶素没食子酸酯及其糖苷对人肠道麦芽糖酶的抑制作用。
Biotechnol Bioprocess Eng. 2012;17(5):966-971. doi: 10.1007/s12257-012-0242-8. Epub 2012 Oct 24.
2
A New Golden Age of Natural Products Drug Discovery.天然产物药物发现的新黄金时代。
Cell. 2015 Dec 3;163(6):1297-300. doi: 10.1016/j.cell.2015.11.031.
3
Evolution of translation machinery in recoded bacteria enables multi-site incorporation of nonstandard amino acids.经过密码子重编码的细菌中翻译机制的进化使得非标准氨基酸能够进行多位点掺入。
Nat Biotechnol. 2015 Dec;33(12):1272-1279. doi: 10.1038/nbt.3372. Epub 2015 Nov 16.
4
Genome-wide identification and evaluation of constitutive promoters in streptomycetes.链霉菌中组成型启动子的全基因组鉴定与评估
Microb Cell Fact. 2015 Oct 29;14:172. doi: 10.1186/s12934-015-0351-0.
5
Ribosome Subunit Stapling for Orthogonal Translation in E. coli.用于大肠杆菌中正交翻译的核糖体亚基订书钉作用
Angew Chem Int Ed Engl. 2015 Oct 19;54(43):12791-4. doi: 10.1002/anie.201506311. Epub 2015 Aug 26.
6
Increasing antibiotic production yields by favoring the biosynthesis of precursor metabolites glucose-1-phosphate and/or malonyl-CoA in Streptomyces producer strains.通过促进链霉菌生产菌株中前体代谢物葡萄糖-1-磷酸和/或丙二酰辅酶A的生物合成来提高抗生素产量。
J Antibiot (Tokyo). 2016 Mar;69(3):179-82. doi: 10.1038/ja.2015.104. Epub 2015 Oct 14.
7
Heterologous coexpression of Vitreoscilla hemoglobin and Bacillus megaterium glucanase in Streptomyces lydicus A02 enhanced its production of antifungal metabolites.在利迪链霉菌A02中异源共表达透明颤菌血红蛋白和巨大芽孢杆菌葡聚糖酶可提高其抗真菌代谢产物的产量。
Enzyme Microb Technol. 2015 Dec;81:80-7. doi: 10.1016/j.enzmictec.2015.08.003. Epub 2015 Aug 12.
8
Exploiting a precise design of universal synthetic modular regulatory elements to unlock the microbial natural products in Streptomyces.利用通用合成模块化调控元件的精确设计来挖掘链霉菌中的微生物天然产物。
Proc Natl Acad Sci U S A. 2015 Sep 29;112(39):12181-6. doi: 10.1073/pnas.1511027112. Epub 2015 Sep 15.
9
Cas9-Assisted Targeting of CHromosome segments CATCH enables one-step targeted cloning of large gene clusters.Cas9辅助靶向染色体片段技术（CATCH）可实现大型基因簇的一步靶向克隆。
Nat Commun. 2015 Sep 1;6:8101. doi: 10.1038/ncomms9101.
10
Highly efficient editing of the actinorhodin polyketide chain length factor gene in Streptomyces coelicolor M145 using CRISPR/Cas9-CodA(sm) combined system.利用 CRISPR/Cas9-CodA(sm) 联合系统对变红红球菌聚酮链长因子基因进行高效编辑。
Appl Microbiol Biotechnol. 2015 Dec;99(24):10575-85. doi: 10.1007/s00253-015-6931-4. Epub 2015 Aug 29.
Zotero 插件