Towards a Synthetic Biology Toolset for Metallocluster Enzymes in Biosynthetic Pathways: What We Know and What We Need

Microbes are routinely engineered to synthesize high-value chemicals from renewable materials through synthetic biology and metabolic engineering. Microbial biosynthesis often relies on expression of heterologous biosynthetic pathways, i.e., enzymes transplanted from foreign organisms. Metallocluste...

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Autores principales:	Helena Shomar, Gregory Bokinsky
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	metallocluster enzymes synthetic biology metabolic engineering heterologous expression FeS cluster electron transfer Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/021319f26cf64130b3a9067d7617218b
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id	oai:doaj.org-article:021319f26cf64130b3a9067d7617218b
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spelling	oai:doaj.org-article:021319f26cf64130b3a9067d7617218b2021-11-25T18:28:31ZTowards a Synthetic Biology Toolset for Metallocluster Enzymes in Biosynthetic Pathways: What We Know and What We Need10.3390/molecules262269301420-3049https://doaj.org/article/021319f26cf64130b3a9067d7617218b2021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/22/6930https://doaj.org/toc/1420-3049Microbes are routinely engineered to synthesize high-value chemicals from renewable materials through synthetic biology and metabolic engineering. Microbial biosynthesis often relies on expression of heterologous biosynthetic pathways, i.e., enzymes transplanted from foreign organisms. Metallocluster enzymes are one of the most ubiquitous family of enzymes involved in natural product biosynthesis and are of great biotechnological importance. However, the functional expression of recombinant metallocluster enzymes in live cells is often challenging and represents a major bottleneck. The activity of metallocluster enzymes requires essential supporting pathways, involved in protein maturation, electron supply, and/or enzyme stability. Proper function of these supporting pathways involves specific protein–protein interactions that remain poorly characterized and are often overlooked by traditional synthetic biology approaches. Consequently, engineering approaches that focus on enzymatic expression and carbon flux alone often overlook the particular needs of metallocluster enzymes. This review highlights the biotechnological relevance of metallocluster enzymes and discusses novel synthetic biology strategies to advance their industrial application, with a particular focus on iron-sulfur cluster enzymes. Strategies to enable functional heterologous expression and enhance recombinant metallocluster enzyme activity in industrial hosts include: (1) optimizing specific maturation pathways; (2) improving catalytic stability; and (3) enhancing electron transfer. In addition, we suggest future directions for developing microbial cell factories that rely on metallocluster enzyme catalysis.Helena ShomarGregory BokinskyMDPI AGarticlemetallocluster enzymessynthetic biologymetabolic engineeringheterologous expressionFeS clusterelectron transferOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6930, p 6930 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	metallocluster enzymes synthetic biology metabolic engineering heterologous expression FeS cluster electron transfer Organic chemistry QD241-441
spellingShingle	metallocluster enzymes synthetic biology metabolic engineering heterologous expression FeS cluster electron transfer Organic chemistry QD241-441 Helena Shomar Gregory Bokinsky Towards a Synthetic Biology Toolset for Metallocluster Enzymes in Biosynthetic Pathways: What We Know and What We Need
description	Microbes are routinely engineered to synthesize high-value chemicals from renewable materials through synthetic biology and metabolic engineering. Microbial biosynthesis often relies on expression of heterologous biosynthetic pathways, i.e., enzymes transplanted from foreign organisms. Metallocluster enzymes are one of the most ubiquitous family of enzymes involved in natural product biosynthesis and are of great biotechnological importance. However, the functional expression of recombinant metallocluster enzymes in live cells is often challenging and represents a major bottleneck. The activity of metallocluster enzymes requires essential supporting pathways, involved in protein maturation, electron supply, and/or enzyme stability. Proper function of these supporting pathways involves specific protein–protein interactions that remain poorly characterized and are often overlooked by traditional synthetic biology approaches. Consequently, engineering approaches that focus on enzymatic expression and carbon flux alone often overlook the particular needs of metallocluster enzymes. This review highlights the biotechnological relevance of metallocluster enzymes and discusses novel synthetic biology strategies to advance their industrial application, with a particular focus on iron-sulfur cluster enzymes. Strategies to enable functional heterologous expression and enhance recombinant metallocluster enzyme activity in industrial hosts include: (1) optimizing specific maturation pathways; (2) improving catalytic stability; and (3) enhancing electron transfer. In addition, we suggest future directions for developing microbial cell factories that rely on metallocluster enzyme catalysis.
format	article
author	Helena Shomar Gregory Bokinsky
author_facet	Helena Shomar Gregory Bokinsky
author_sort	Helena Shomar
title	Towards a Synthetic Biology Toolset for Metallocluster Enzymes in Biosynthetic Pathways: What We Know and What We Need
title_short	Towards a Synthetic Biology Toolset for Metallocluster Enzymes in Biosynthetic Pathways: What We Know and What We Need
title_full	Towards a Synthetic Biology Toolset for Metallocluster Enzymes in Biosynthetic Pathways: What We Know and What We Need
title_fullStr	Towards a Synthetic Biology Toolset for Metallocluster Enzymes in Biosynthetic Pathways: What We Know and What We Need
title_full_unstemmed	Towards a Synthetic Biology Toolset for Metallocluster Enzymes in Biosynthetic Pathways: What We Know and What We Need
title_sort	towards a synthetic biology toolset for metallocluster enzymes in biosynthetic pathways: what we know and what we need
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/021319f26cf64130b3a9067d7617218b
work_keys_str_mv	AT helenashomar towardsasyntheticbiologytoolsetformetalloclusterenzymesinbiosyntheticpathwayswhatweknowandwhatweneed AT gregorybokinsky towardsasyntheticbiologytoolsetformetalloclusterenzymesinbiosyntheticpathwayswhatweknowandwhatweneed
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Towards a Synthetic Biology Toolset for Metallocluster Enzymes in Biosynthetic Pathways: What We Know and What We Need

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