Jia Bao Zhang, Wei Chen, Yong Jun Yang and Zhen Zhen Liu
{"title":"Discovery and green metabolic engineering of a self-sufficient genistein pathway in Paenibacillus jilinensis†","authors":"Jia Bao Zhang, Wei Chen, Yong Jun Yang and Zhen Zhen Liu","doi":"10.1039/D5GC01323B","DOIUrl":null,"url":null,"abstract":"<p >Genistein, a plant-derived isoflavone with pharmaceutical value, is conventionally obtained through ecologically detrimental extraction processes that rely on large-scale plant harvesting and hazardous solvents. Here, we report the discovery of native genistein biosynthesis in the <em>Paenibacillus jilinensis</em>, which inherently produces 5.7 mg L<small><sup>−1</sup></small> genistein <em>via</em> the phenylalanine branch of the phenylpropanoid pathway. This pathway mirrors plant flavonoid synthesis but operates through seven bacterial enzymes (<em>Pj</em>PAL, <em>Pj</em>C4H, <em>Pj</em>4CL, <em>Pj</em>CHS, <em>Pj</em>CHI, <em>Pj</em>IFS, and <em>Pj</em>HID) with about 30% sequence homology to the corresponding protein sequences in plants, suggesting evolutionary convergence. To leverage this native capability for sustainable production, we constructed a genome-scale metabolic model (GSMM YPG26) with 1636 reactions and 717 genes to rationally optimize carbon flux. Metabolic engineering elevated genistein titers by 9.3-fold to 52.8 mg L<small><sup>−1</sup></small> without introducing heterologous plant genes. Green-chemistry analysis further showed that <em>P. jilinensis</em>-ΔGLN achieves 92% less waste than soybean extraction and up to one order of magnitude better than state-of-the-art <em>E. coli</em> and yeast systems. It is crucial that this bacterial platform requires only a basic culture medium for sustained production, and eliminates dependence on medicinal plants. Our findings reveal <em>P. jilinensis</em> as a naturally gifted genistein producer and a green chassis for industrial isoflavone synthesis, aligning with green chemistry goals of waste prevention and bio-based process innovation.</p>","PeriodicalId":78,"journal":{"name":"Green Chemistry","volume":" 25","pages":" 7575-7585"},"PeriodicalIF":9.3000,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Green Chemistry","FirstCategoryId":"92","ListUrlMain":"https://pubs.rsc.org/en/content/articlelanding/2025/gc/d5gc01323b","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
Genistein, a plant-derived isoflavone with pharmaceutical value, is conventionally obtained through ecologically detrimental extraction processes that rely on large-scale plant harvesting and hazardous solvents. Here, we report the discovery of native genistein biosynthesis in the Paenibacillus jilinensis, which inherently produces 5.7 mg L−1 genistein via the phenylalanine branch of the phenylpropanoid pathway. This pathway mirrors plant flavonoid synthesis but operates through seven bacterial enzymes (PjPAL, PjC4H, Pj4CL, PjCHS, PjCHI, PjIFS, and PjHID) with about 30% sequence homology to the corresponding protein sequences in plants, suggesting evolutionary convergence. To leverage this native capability for sustainable production, we constructed a genome-scale metabolic model (GSMM YPG26) with 1636 reactions and 717 genes to rationally optimize carbon flux. Metabolic engineering elevated genistein titers by 9.3-fold to 52.8 mg L−1 without introducing heterologous plant genes. Green-chemistry analysis further showed that P. jilinensis-ΔGLN achieves 92% less waste than soybean extraction and up to one order of magnitude better than state-of-the-art E. coli and yeast systems. It is crucial that this bacterial platform requires only a basic culture medium for sustained production, and eliminates dependence on medicinal plants. Our findings reveal P. jilinensis as a naturally gifted genistein producer and a green chassis for industrial isoflavone synthesis, aligning with green chemistry goals of waste prevention and bio-based process innovation.
期刊介绍:
Green Chemistry is a journal that provides a unique forum for the publication of innovative research on the development of alternative green and sustainable technologies. The scope of Green Chemistry is based on the definition proposed by Anastas and Warner (Green Chemistry: Theory and Practice, P T Anastas and J C Warner, Oxford University Press, Oxford, 1998), which defines green chemistry as the utilisation of a set of principles that reduces or eliminates the use or generation of hazardous substances in the design, manufacture and application of chemical products. Green Chemistry aims to reduce the environmental impact of the chemical enterprise by developing a technology base that is inherently non-toxic to living things and the environment. The journal welcomes submissions on all aspects of research relating to this endeavor and publishes original and significant cutting-edge research that is likely to be of wide general appeal. For a work to be published, it must present a significant advance in green chemistry, including a comparison with existing methods and a demonstration of advantages over those methods.