A polyketide-based biosynthetic platform for diols, amino alcohols and hydroxy acids

IF 42.8 1区化学 Q1 CHEMISTRY, PHYSICAL Nature Catalysis Pub Date : 2025-02-11 DOI:10.1038/s41929-025-01299-5

Qingyun Dan, Yan Chiu, Namil Lee, Jose Henrique Pereira, Behzad Rad, Xixi Zhao, Kai Deng, Yiou Rong, Chunjun Zhan, Yan Chen, Seokjung Cheong, Chenyi Li, Jennifer W. Gin, Andria Rodrigues, Trent R. Northen, Tyler W. H. Backman, Edward E. K. Baidoo, Christopher J. Petzold, Paul D. Adams, Jay D. Keasling

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Abstract

Medium- and branched-chain diols and amino alcohols are important industrial solvents, polymer building blocks, cosmetics and pharmaceutical ingredients, yet biosynthetically challenging to produce. Here we present an approach that uses a modular polyketide synthase (PKS) platform for the efficient production of these compounds. This platform takes advantage of a versatile loading module from the rimocidin PKS and nicotinamide adenine dinucleotide phosphate-dependent terminal thioreductases. Reduction of the terminal aldehyde with alcohol dehydrogenases enables the production of diols, oxidation enables the production of hydroxy acids and specific transaminases allow the production of various amino alcohols. Furthermore, replacement of the malonyl-coenzyme A-specific acyltransferase in the extension module with methyl- or ethylmalonyl-coenzyme A-specific acyltransferase enables the production of branched-chain diols, amino alcohols and carboxylic acids in high titres. Use of our PKS platform in Streptomyces albus demonstrated the high tunability and efficiency of the platform.

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来源期刊

Nature Catalysis Chemical Engineering-Bioengineering

CiteScore

52.10

自引率

1.10%

发文量

140

期刊介绍： Nature Catalysis serves as a platform for researchers across chemistry and related fields, focusing on homogeneous catalysis, heterogeneous catalysis, and biocatalysts, encompassing both fundamental and applied studies. With a particular emphasis on advancing sustainable industries and processes, the journal provides comprehensive coverage of catalysis research, appealing to scientists, engineers, and researchers in academia and industry. Maintaining the high standards of the Nature brand, Nature Catalysis boasts a dedicated team of professional editors, rigorous peer-review processes, and swift publication times, ensuring editorial independence and quality. The journal publishes work spanning heterogeneous catalysis, homogeneous catalysis, and biocatalysis, covering areas such as catalytic synthesis, mechanisms, characterization, computational studies, nanoparticle catalysis, electrocatalysis, photocatalysis, environmental catalysis, asymmetric catalysis, and various forms of organocatalysis.