Methods of producing 7-carbon chemicals via c1 carbon chain elongation associated with coenzyme B synthesis

摘要

This document describes biochemical pathways for producing pimelic acid, 7-aminoheptanoic acid, 7-hydroxyheptanoic acid, heptamethylenediamine or 1,7-heptanediol by forming one or two terminal functional groups, each comprised of carboxyl, amine or hydroxyl group, in a C7 aliphatic backbone substrate. These pathways, metabolic engineering and cultivation strategies described herein rely on the C1 elongation enzymes or homolog associated with coenzyme B biosynthesis.

主权项

1. A method for biosynthesizing pimelic acid, 7-aminoheptanoate, 7-hydroxyheptanoate, or heptamethylenediamine, said method comprising:
(i) three cycles of 2-oxoacid chain elongation comprising contacting 2-oxoglutarate with a (homo)ncitrate synthase classified under EC 2.3.3.14 or 2.3.3.13, a (homo)ncitrate dehydratase classified under EC 4.2.1.114, 4.2.1.36, or 4.2.1.33, a (homo)naconitate hydratase, and an iso(homo)ncitrate dehydrogenase classified under EC 1.1.85, 1.1.87, or 1.1.1.286, to form 2-oxosuberate; (ii) contacting said 2-oxosuberate with an indolepyruvate decarboxylase to form pimelate semialdehyde or contacting said 2-oxosuberate with a 2-oxoglutarate dehydrogenase complex to form pimeloyl-CoA; and (iii) contacting said pimelate semialdehyde or said pimeloyl-CoA with a thioesterase classified under EC 3.1.2, an aldehyde dehydrogenase classified under EC 1.2.1.3, a 7-oxoheptanoate dehydrogenase classified under EC 1.2.1, a 6-oxohexanoate dehydrogenase classified under EC 1.2.1, a glutaconoate CoA-transferase classified under EC 2.8.3.12, a reversible succinyl-CoA-ligase classified under EC 6.2.1.5, or an alcohol dehydrogenase classified under EC 1.1.1.- to form pimelic acid or 7-hydroxyheptanoate; and/or contacting said pimelate semialdehyde or said pimeloyl-CoA with an ω-transaminase classified under EC 2.6.1.18, 2.6.1.19, 2.6.1.29, 2.6.1.48, or 2.6.1.82, or a deacetylase classified under EC 3.5.1.62 to form 7-aminoheptanoate or heptamethylenediamine.