Article
Plant Sciences
Lijuan Wang, Mengyi Zhu, Qingbo Zhang, Shilan Zhai, Yiguang Zhu, Haibo Zhang, Changsheng Zhang
Summary: In this study, an alternative biological route to produce structurally diverse fidaxomicin aglycones was developed by refactoring the promoter and expressing it in a different host. The resulting titers of the five fidaxomicin aglycones ranged from 4.9 to 15.0 mg L-1. Overall, these findings demonstrate the potential of using a biological strategy to construct and diversify fidaxomicin aglycones.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Chemistry, Organic
Blaise Kimbadi Lombe, Lea Winand, Jan Diettrich, Melanie Tobermann, Wolf Hiller, Marcel Kaiser, Markus Nett
Summary: In this study, we report the discovery of massinidine, an aguanidine alkaloid with antiplasmodial activity, from bacteria of the genus Massilia. The biosynthetic genes of massinidine were identified and validated through heterologous expression. Bioinformatic analysis reveals the widespread potential for massinidine biosynthesis in various proteobacteria.
Review
Biochemical Research Methods
Lei Li, Logan W. Maclntyre, Sean F. Brady
Summary: This review summarizes recent advances in heterologous production of bacterial and fungal NPs, with a focus on next-generation transcriptional regulatory modules, novel BGC refactoring techniques, and optimized heterologous hosts.
CURRENT OPINION IN BIOTECHNOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Takahisa Kogure, Masako Suda, Kazumi Hiraga, Masayuki Inui
Summary: Protocatechuic acid (PCA) is a natural bioactive phenolic acid that can be produced by Corynebacterium glutamicum through the DHS and 4-HBA pathways. Simultaneous utilization of both pathways is an efficient method for PCA production, with the highest reported productivity reaching 82.7 g/L.
METABOLIC ENGINEERING
(2021)
Article
Plant Sciences
Xingxing Wei, Tsz Ki Chan, Che Tung Derek Kong, Yudai Matsuda
Summary: The biosynthetic gene cluster for the cyclic heptapeptides unguisins A and B, which contain the neurotransmitter gamma-aminobutyric acid (GABA), was discovered in the fungus Aspergillus violaceofuscus CBS 115571. Enzymatic reactions and gene deletion experiments showed that the unguisin pathway involves the alanine racemase UngC to produce D-alanine, which is then utilized by the first adenylation domain of the nonribosomal peptide synthetase UngA. Surprisingly, the hydrolase UngD was found to convert unguisins into previously unknown linear peptides. Heterologous production of these peptides was achieved in Aspergillus oryzae, and genome mining revealed new unguisin variants, each containing a (2R,3R)-beta-methylphenylalanine residue.
JOURNAL OF NATURAL PRODUCTS
(2023)
Review
Biotechnology & Applied Microbiology
Balwant S. Paliya, Vivek K. Sharma, Maria G. Tuohy, Harikesh B. Singh, Mattheos Koffas, Rachid Benhida, Brijesh K. Tiwari, Deepak M. Kalaskar, Brahma N. Singh, Vijai K. Gupta
Summary: The recent development in human glycome and glycosylation pathways has allowed the incorporation of suitable machinery for protein modification in non-natural hosts, creating opportunities for constructing next-generation tailored glycans and glycoconjugates. Bacterial metabolic engineering enables the production of tailored bio-polymers using living microbial factories as whole-cell biocatalysts, providing a cost-effective means for producing valuable polysaccharides in bulk quantities for practical applications.
BIOTECHNOLOGY ADVANCES
(2023)
Article
Biochemistry & Molecular Biology
Hanyu Liang, Hongjuan Chen, Xinya Liu, Zihan Wang, Pengfu Li, Shan Lu
Summary: This study aims to investigate the synthesis mechanism of astaxanthin and suggests that the hydroxylation step may be the bottleneck for heterologous production of astaxanthin in Synechocystis.
Article
Biochemistry & Molecular Biology
Young-Jin Son, Hee-Jong Hwang, Yonghoon Kwon
Summary: This study reports the scalable biosynthesis and full structural characterization of thiocillin IV, a 26-membered thiopeptide. By inserting the tclO gene and genes responsible for micrococcin P2 production into a Bacillus strain, researchers achieved a production of 2.4 mg/L of culture. The purified thiocillin IV structure was identified as O-methylated micrococcin P2 at the 8-Thr position, showing promising biological activity against various Gram-positive pathogens.
ACS CHEMICAL BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Dongsoo Yang, Hyunmin Eun, Cindy Pricilia Surya Prabowo
Summary: Polyketides, a type of natural products, have versatile applications such as pharmaceuticals, nutraceuticals, and cosmetics. Aromatic polyketides, including type II and III polyketides, are important chemicals for human health, such as antibiotics and anticancer agents. However, they are mainly produced from challenging sources like soil bacteria or plants. To address this issue, metabolic engineering and synthetic biology have been used to efficiently engineer model microorganisms for enhanced production of aromatic polyketides. This review discusses the recent advancements and future prospects of metabolic engineering and synthetic biology strategies in the production of type II and type III polyketides in model microorganisms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biotechnology & Applied Microbiology
Liangyu Lu, Xiaolei Wang, Lei Zhou, Qiyuan Liu, Guanghao Zhang, Bingqing Xue, Chenyu Hu, Xiaolin Shen, Xinxiao Sun, Yajun Yan, Jia Wang, Qipeng Yuan
Summary: In this study, a biosynthetic pathway was designed and constructed in E. coli for the de novo production of p-Hydroxyacetophenone (p-HAP) and its glucoside picein from glucose. The rate-limiting step in the pathway was eliminated by modulating intracellular redox cofactors, resulting in a high production of p-HAP. A novel p-HAP glucosyltransferase capable of generating picein was also identified and characterized. The successful biosynthesis of picein from glucose demonstrates the potential of this pathway design strategy for producing valuable compounds.
METABOLIC ENGINEERING
(2023)
Article
Biotechnology & Applied Microbiology
Luciana Fernandes Brito, Marta Irla, Ingemar Naerdal, Simone Balzer Le, Baudoin Delepine, Stephanie Heux, Trygve Brautaset
Summary: This study successfully established a method for methanol-based production of 5-aminovalerate (5AVA) using recombinant Bacillus methanolicus strains. Among the five tested biosynthesis pathways, two pathways achieved the highest titer of 0.02 g l(-1) 5AVA production, making it the first report of 5AVA production from methanol in methylotrophic bacteria.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2021)
Review
Biochemical Research Methods
Muhammad Saad Ahmed, Kyle J. Lauersen, Sana Ikram, Chun Li
Summary: This study provides insights into efflux transport proteins as potential solutions for enhancing the export of heterologous metabolites from microbial cell systems, including their mechanistic modes of action, selection of appropriate transporters, and future research directions.
ACS SYNTHETIC BIOLOGY
(2021)
Article
Agriculture, Multidisciplinary
Yali Duan, Jiawei Liu, Yun Du, Xiaolin Pei, Mu Li
Summary: The study successfully developed a high nepetalactol-producing Aspergillus oryzae platform strain by co-expressing 5 nepetalactol biosynthetic genes in a high isopentenyl pyrophosphate (IPP) producing strain, achieving the biosynthesis of nepetalactol and improving IPP supply while suppressing the byproduct citronellol formation. The engineered strain achieved the highest titer of nepetalactol after optimization of the carbon source, representing the highest reported titer in microbial cells.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2021)
Review
Biotechnology & Applied Microbiology
Jiaqi Liu, Guangzhi Dai, Youming Zhang, Xiaoying Bian
Summary: This review article discusses the latest advances in synthetic biology tools and strategies for optimizing secondary metabolite production in non-model microorganisms. The importance of developing broader non-model microbial chassis as programmable heterologous hosts is highlighted, along with the successful applications of heterologous production of complex secondary metabolites. The perspective of developing ideal cell factories in the artificial intelligence-driven genome era is also emphasized.
BIOTECHNOLOGY ADVANCES
(2022)
Article
Agriculture, Multidisciplinary
Chunyang Cao, Haiyan Zhang, Xuan Cao, Sijia Kong, Beiwei Zhu, Xinping Lin, Yongjin J. Zhou
Summary: Engineering microorganisms to synthesize isoprenoids is an efficient approach to increase their concentration. In this study, three types of isoprenoid pathways were constructed and optimized in yeast peroxisomes to produce the sesquiterpene (+)-valencene. The Haloarchaea-type MVA pathway was found to be more effective, and a production of 869 mg/L (+)-valencene was achieved. This work expands isoprenoid synthesis in eukaryotes and provides a more efficient pathway for isoprenoid production.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)