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

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 a novel approach utilising 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 NADPH-dependent terminal thioreductases (TRs), previously untapped in engineered PKSs. Reduction of the terminal aldehyde with specific alcohol dehydrogenases enables production of diols, oxidation enables production of hydroxy acids, and transamination with specific transaminases enables production of various amino alcohols. Furthermore, replacement of the malonyl-coenzyme A (CoA)–specific acyltransferase (AT) in the extension module with methyl- or ethylmalonyl-CoA–specific ATs enables production of branched-chain diols and amino alcohols. In total, we demonstrated production of nine 1,3-diols (including the difficult-to-produce insect repellent and cosmetic ingredient 2-ethyl-1,3-hexanediol), six amino alcohols, and two carboxylic acids using our PKS platform in Streptomyces albus. Finally, tuning production of the PKS acyl-CoA substrates enabled production of high titers of specific diols and amino alcohols (1 g/L diol titer in shake flasks), demonstrating high tunability and efficiency of the platform.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Streptomyces Albus

SUBMITTER: Christopher Petzold

LAB HEAD: Christopher J. Petzold

PROVIDER: PXD055149 | Pride | 2024-12-02

REPOSITORIES: Pride

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			Action	DRS
	Control-R1.raw	Raw
	Control-R2.raw	Raw
	Control-R3.raw	Raw
	Dan_et_al_Proteomics_set1.csv	Csv
	Dan_et_al_Proteomics_set2.csv	Csv

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

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