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Genetic manipulation of secondary metabolite biosynthesis for improved production in Streptomyces and other actinomycetes

  • Natural Products
  • Published:
Journal of Industrial Microbiology & Biotechnology

Abstract

Actinomycetes continue to be important sources for the discovery of secondary metabolites for applications in human medicine, animal health, and crop protection. With the maturation of actinomycete genome mining as a robust approach to identify new and novel cryptic secondary metabolite gene clusters, it is critical to continue developing methods to activate and enhance secondary metabolite biosynthesis for discovery, development, and large-scale manufacturing. This review covers recent reports on promising new approaches and further validations or technical improvements of existing approaches to strain improvement applicable to a wide range of Streptomyces species and other actinomycetes.

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Abbreviations

Act:

Actinorhodin

att/int:

Attachment/integration

AmR:

Apramycin resistance or resistance gene

Ant:

Antimycin

AUD:

Amplifiable unit of DNA

Ave:

Avermectin

Blm:

Bleomycin

CDA:

Calcium-dependent antibiotic

CDS:

Protein coding sequence

Cdn:

Candicidin

Cch:

Coelichelin

Cml:

Chloramphenicol

Cpk:

Coelimycin

Erm:

Erythromycin

ermEp*:

Strong constitutive promoter derived from the ermE gene

FAS:

Fatty acid synthase

Fdm:

Fredericamycin

LAL:

Large ATP-binding regulator of the LuxR family

Kin:

Kinamycin

Nat:

Natamycin

Net:

Netropsin (congocidin)

Nys:

Nystatin

NRP:

Nonribosomal peptide

NRPS:

Nonribosomal peptide synthetase

Olm:

Oligomycin

PAS:

Signaling domain of regulatory protein

Pim:

Pimaricin

PK:

Polyketide

PKS:

Polyketide synthase

Pte:

Filipin

PPTase:

Phosphopantetheinyl transferase

PTM:

Polycyclic tetramate macrolactam

Red:

Undecylprodigiosyn

Rap:

Rapamycin

Rif:

Rifampicin or rifamycin

RifR:

Rifampicin resistant

RiPP:

Ribosomally synthesized and post-translationally modified peptide

SARP:

Streptomyces antibiotic regulatory protein

SM:

Secondary metabolite

SMGC:

Secondary metabolite gene cluster

SpcR:

Spectinomycin resistant

Srm:

Spiramycin

Stm:

Stambomycin

Str:

Streptomycin

StrR:

Streptomycin resistant

TIR:

Terminal inverted repeat

Tpn:

Teicoplanin

ts:

Temperature sensitive

Tsr:

Thiostrepton

Tyl:

Tylosin

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    Richard H. Baltz

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Special Issue: Natural Product Discovery and Development in the Genomic Era. Dedicated to Professor Satoshi Ōmura for his numerous contributions to the field of natural products.

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Baltz, R.H. Genetic manipulation of secondary metabolite biosynthesis for improved production in Streptomyces and other actinomycetes. J Ind Microbiol Biotechnol 43, 343–370 (2016). https://doi.org/10.1007/s10295-015-1682-x

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